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The deltex family protein DTX3 is believed to possess E3 ubiquitin ligase activity, as it contains a classic RING finger domain. However, its biological role and the underlying mechanism in cancer remain largely elusive. Here, we identified DTX3 as a novel mutant p53-interacting protein in ovarian carcinoma. Mechanistically, DTX3 mediated mutant p53 ubiquitination and stabilization by perturbing the MDM2-mutant p53 interaction, consequently leading to activation of diverse mutant p53 target genes. Importantly, a positive correlation between the expression of DTX3 and mutant p53 target genes was further validated in ovarian carcinomas. Ectopic DTX3 promoted, while depletion of DTX3 suppressed, ovarian cancer cell proliferation and invasion. Remarkably, the pro-tumorigenic effect of DTX3 is dependent on mutant p53, because ablation of mutant p53 significantly impaired DTX3-induced gene expression and ovarian cancer cell growth and propagation. Furthermore, DTX3 elevated the expression of mutant p53 target genes and boosted ovarian tumor growth in vivo. Finally, DTX3 was amplified and overexpressed in ovarian carcinomas, which is significantly associated with unfavorable prognosis. Altogether, our findings unveil the oncogenic role of DTX3 in ovarian cancer development by bolstering mutant p53 activity.

Publication of the complete genome sequence of Arabidopsis thaliana, the first plant reference genome, in December 2000 heralded the beginning of the plant genome era. Over the past 20 years reference genomes have been generated for hundreds of plant species, spanning non-vascular to flowering plants. Releasing these plant genomes has dramatically advanced studies in all disciplines of plant biology. Importantly, multiple reference-level genomes have been generated for the major crops and their progenitors, enabling the creation of pan-genomes and exploration of domestication history and natural variations that can be adopted by modern crop breeding. We summarize the progress of plant genome sequencing and the challenges of sequencing more complex plant genomes and generating pan-genomes.

Circular RNA (circRNA) is a kind of new regulatory RNA with diverse biological functions. Numerous circRNAs have been identified in many plant species; however, evolution of plant circRNAs remains largely unknown. In this study, we assembled full-length sequences of 6,519 rice (Oryza sativa) circRNAs and analyzed their conservation in other 46 plant species based on comparison of sequences and expression patterns. We found that, at the genomic level, 8.7% of the 6,519 circRNAs were conserved in dicotyledonous plants and 49.1% in Oryza genus. Meanwhile, 57.8% of parental protein coding genes of the rice circRNAs originated recently after divergence of monocotyledonous plants, implying recent origin of the majority of rice circRNAs, a conclusion further supported by the results based on analysis of 4,663 full-length circRNAs in Arabidopsis thaliana. Accordingly, we proposed three models to address the origination of different types of circRNAs. Taken together, the results obtained in this study provide new insights for the evolutionary dynamics of plant circRNAs and candidate circRNAs for further functional exploration.

Background: Peripheral blood CD4+ T cell counts are a clinical marker for assessing disease progression in HIV-infected patients as well as in SIV-/SHIV–infected macaques. However, it is clinically debatable about whether this marker is a sole indicator for assessing HIV disease progression and need for ART in HIV-infected individuals. Studies with SIV-or SHIV-infected Indian rhesus macaques and sooty mangabeys have generated the conflicting data regarding the association of CD4+ T cell depletion with viral loads and disease progression. Results: In the present study, we used cynomolgus monkeys, a suitable non-human primate model for chronic HIV infection studies, to determine the effects of the antibody-mediated acute CD4+ cell depletion on viral load as well as on the immunological factors associated with disease progression. We found that as compared with the control animals, CD4+ T cell-depleted animals with chronic SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4+ T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. Conclusions: These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys. Future investigations are necessary to identify novel and more reliable clinical markers correlated with viremia and disease progression in HIV-infected individuals.

Approximately 80% of human pancreatic ductal adenocarcinomas (PDAC) harbor TP53 mutations, among which, R273H is the most frequent. Although p53-R273H is known to possess gain-of-function properties, how it is regulated in PDAC has not been extensively explored. Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation-tandem mass spectrometry analysis. VCP bound p53-R273H at its DNA binding domain. Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. Consistently, ablation of VCP markedly retarded growth of cultured PDAC cells and xenograft PDAC tumors. Together, these results unveil VCP as a novel partner of p53-R273H in promoting PDAC growth and as a potential target for developing anti-PDAC therapy. Significance: These findings identify valosin-containing protein (VCP) as a novel regulator of p53-R273H stability and suggest VCP as a potential target for development of pancreatic cancer therapy.

Rice is one of cereal crops and a model species for monocots. Since the release of the first draft rice genome sequences in 2002, considerable progress has been achieved in rice genomic researches, thanks to rapid development and efficient utilization of bioinformatics methods and tools. In this review, we summarize the progress of studies of rice genome sequencing and other omics and introduce the well-maintained bioinformatics databases and tools developed for rice genome resources and breeding. After reviewing the history of rice bioinformatics, we use single-cell sequencing and machine learning as examples showing how bioinformatics integrates emerging technologies and how it continues to develop for future rice research.

Background Phytophthora capsici root rot (PRR) is a disastrous disease in peppers (Capsicum spp.) caused by soilborne oomycete with typical symptoms of necrosis and constriction at the basal stem and consequent plant wilting. Most studies on the QTL mapping of P. capsici resistance suggested a consensus broad-spectrum QTL on chromosome 5 named Pc.5.1 regardless of P. capsici isolates and resistant resources. In addition, all these reports proposed NBS-ARC domain genes as candidate genes controlling resistance. Results We screened out 10 PRR-resistant resources from 160 Capsicum germplasm and inspected the response of locus Pc.5.1 and NBS-ARC genes during P. capsici infection by comparing the root transcriptomes of resistant pepper 305R and susceptible pepper 372S. To dissect the structure of Pc.5.1, we anchored genetic markers onto pepper genomic sequence and made an extended Pc5.1 (Ext-Pc5.1) located at 8.35 Mb–38.13 Mb on chromosome 5 which covered all Pc5.1 reported in publications. A total of 571 NBS-ARC genes were mined from the genome of pepper CM334 and 34 genes were significantly affected by P. capsici infection in either 305R or 372S. Only 5 inducible NBS-ARC genes had LRR domains and none of them was positioned at Ext-Pc5.1. Ext-Pc5.1 did show strong response to P. capsici infection and there were a total of 44 differentially expressed genes (DEGs), but no candidate genes proposed by previous publications was included. Snakin-1 (SN1), a well-known antimicrobial peptide gene located at Pc5.1, was significantly decreased in 372S but not in 305R. Moreover, there was an impressive upregulation of sugar pathway genes in 305R, which was confirmed by metabolite analysis of roots. The biological processes of histone methylation, histone phosphorylation, DNA methylation, and nucleosome assembly were strongly activated in 305R but not in 372S, indicating an epigenetic-related defense mechanism. Conclusions Those NBS-ARC genes that were suggested to contribute to Pc5.1 in previous publications did not show any significant response in P. capsici infection and there were no significant differences of these genes in transcription levels between 305R and 372S. Other pathogen defense-related genes like SN1 might account for Pc5.1. Our study also proposed the important role of sugar and epigenetic regulation in the defense against P. capsici.

Background Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. Results In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5–15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10–60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25–50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. Conclusions These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

Weeds and weedy rice plague commercial rice fields in many countries. Developing herbicide-tolerance rice is the most efficient strategy to control weed proliferation. CRISPR/Cas9-mediated gene editing, which generates small InDels and nucleotide substitutions at and around target sites using error-prone non-homologous end joining DNA repairing, has been widely adopted for generation of novel crop germplasm with a wide range of genetic variation in important agronomic traits. We created a novel herbicide-tolerance allele in rice by targeting the acetolactate synthase (OsALS) gene using CRISPR/Cas9-mediated gene editing. The novel allele (G628W) arose from a G-to-T transversion at position 1882 of OsALS and conferred a high level of herbicide tolerance. Transgene-free progeny carrying homozygous G628W allele were identified and showed agronomic performance similar to that of wild-type plants, suggesting that the G628W allele is a valuable resource for developing elite rice varieties with strong herbicide tolerance. To promote use of the G628W allele and to accelerate introgression and/or pyramiding of the G628W allele with other elite alleles, we developed a DNA marker for the G628W allele that accurately and robustly distinguished homozygous from heterozygous segregants. Our result further demonstrates the feasibility of CRISPR/Cas9-mediated gene editing in creating novel genetic variation for crop breeding.

Fiber length is one of the most important quality parameters of cotton fibers. Transcriptomic analyses of developing cotton fibers have identified genes preferentially expressing in fiber elongation stage, but few have been functionally characterized. Here, on the basis of confirmation of the preferential expression profile of GhAlaRP (Gh_A09G1166 and Gh_D09G1172), an alanine rich protein gene, in the rapid elongating fibers, we investigated the role of GhAlaRP in fiber development by generating transgenic cottons with an increased or decreased expression level of GhAlaRP. Our results showed that the fiber length was consistently significantly shorter in both the GhAlaRP-RNAi lines and the alarp mutant generated by genome editing than in the control YZ-1. GhAlaRP was localized on plasma membrane, nucleus and endoplasmic reticulum. The yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that GhAlaRP co-expresses and interacts with GhAnnexin (Gh_D11G2184) and GhEXPA (Gh_A10G2323) that are involved in fiber elongation. Down-regulation of GhAlaRP co-suppressed the expression levels of GhAnnexin and GhEXPA. These results suggest a role of GhAlaRP in regulation of cotton fiber elongation, which could be achieved by regulating the functions of GhAnnexin and GhEXPA.

Verticillium wilt is a vascular disease causing tremendous damage to cotton production worldwide. However, our knowledge of the mechanisms of cotton resistance or susceptibility to this disease is very limited. In this study, we compared the defense transcriptomes of cotton (Gossypium hirsutum) cultivars Shidalukang 1 (Verticillium dahliae resistant, HR) and Junmian 1 (V. dahliae susceptible, HS) before and after V. dahliae infection, identified hub genes of the network associated with responses to V. dahliae infection, and functionally characterized one of the hub genes involved in biosynthesis of lignin and phenolics. We identified 6,831 differentially expressed genes (DEGs) between the basal transcriptomes of HR and HS; 3,685 and 3,239 of these DEGs were induced in HR and HS, respectively, at different time points after V. dahliae infection. KEGG pathway analysis indicated that DEGs were enriched for genes involved in lignin biosynthesis. In all, 23 hub genes were identified based on a weighted gene coexpression network analysis of the 6,831 DEGs and their expression profiles at different time points after V. dahliae infection. Knockdown of Gh4CL30, one of the hub genes related to the lignin biosynthesis pathway, by virus-induced gene silencing, led to a decreased content of flavonoids, lignin, and S monomer but an increased content of G monomer, G/S lignin monomer, caffeic acid, and ferulic acid, and enhanced cotton resistance to V. dahliae. These results suggest that Gh4CL30 is a key gene modulating the outputs of different branches of the lignin biosynthesis pathway, and provide new insights into cotton resistance to V. dahliae. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Fiber mutants are unique and valuable resources for understanding the genetic and molecular mechanisms controlling initiation and development of cotton fibers that are extremely elongated single epidermal cells protruding from the seed coat of cottonseeds. In this study, we reported a new fuzzless-tufted cotton mutant (Gossypium hirsutum) and showed that fuzzless-tufted near-isogenic lines (NILs) had similar agronomic traits and a higher ginning efficiency compared to their recurrent parents with normal fuzzy seeds. Genetic analysis revealed that the mutant phenotype is determined by a single incomplete dominant locus, designated N5. The mutation was fine mapped to an approximately 250-kb interval containing 33 annotated genes using a combination of bulked segregant sequencing, SNP chip genotyping, and fine mapping. Comparative transcriptomic analysis using 0–6 days post-anthesis (dpa) ovules from NILs segregating for the phenotypes of fuzzless-tufted (mutant) and normal fuzzy cottonseeds (wild-type) uncovered candidate genes responsible for the mutant phenotype. It also revealed that the flanking region of the N5 locus is enriched with differentially expressed genes (DEGs) between the mutant and wild-type. Several of those DEGs are members of the gene families with demonstrated roles in cell initiation and elongation, such as calcium-dependent protein kinase and expansin. The transcriptome landscape of the mutant was significantly reprogrammed in the 6 dpa ovules and, to a less extent, in the 0 dpa ovules, but not in the 2 and 4 dpa ovules. At both 0 and 6 dpa, the reprogrammed mutant transcriptome was mainly associated with cell wall modifications and transmembrane transportation, while transcription factor activity was significantly altered in the 6 dpa mutant ovules. These results imply a similar molecular basis for initiation of lint and fuzz fibers despite certain differences.

B-cell CLL/lymphoma 7 protein family member C (BCL7C) located at chromosome 16p11.2 shares partial sequence homology with the other two family members, BCL7A and BCL7B. Its role in cancer remains completely unknown. Here, we report our finding of its tumor-suppressive role in ovarian cancer. Supporting this is that BCL7C is downregulated in human ovarian carcinomas, and its underexpression is associated with unfavorable prognosis of ovarian cancer as well as some other types of human cancers. Also, ectopic BCL7C restrains cell proliferation and invasion of ovarian cancer cells. Consistently, depletion of BCL7C reduces apoptosis and promotes cell proliferation and invasion of these cancer cells. Mechanistically, BCL7C suppresses mutant p53-mediated gene transcription by binding to mutant p53, while knockdown of BCL7C enhances the expression of mutant p53 target genes in ovarian cancer cells. Primary ovarian carcinomas that sustain low levels of BCL7C often show the elevated expression of mutant p53 target genes. In line with these results, BCL7C abrogates mutant p53-induced cell proliferation and invasion, but had no impact on proliferation and invasion of cancer cells with depleted p53 or harboring wild-type p53. Altogether, our results demonstrate that BCL7C can act as a tumor suppressor to prevent ovarian tumorigenesis and progression by counteracting mutant p53 activity.

Background Family with sequence similarity 234 member B (FAM234B), a protein-coding gene, is mainly expressed in brain tissues. Its clinical significance and biological function in tumors, especially in breast cancer (BC), have not been elucidated. Methods We firstly investigated the expression pattern of FAM234B at the mRNA and protein levels using Oncomine, TCGA portal, GEPIA, TIMER, HPA, and UALCAN databases, then applied bc-GenExMiner to assess the associations between expression level of FAM234B and clinicopathological features of BC. Besides, we also verified the expression of FAM234B expression in clinical BC samples using qRT-PCR. Subsequently, GEPIA, bc-GenExMiner, and TIMER databases were used to analyze the prognostic significance of FAM234B in all BC and different molecular subtypes. Finally, we conducted co-expression analysis and gene set enrichment analysis (GSEA). Additionally, we explored the regulatory mechanism of FAM234B in BC. Results Both bioinformatics analysis and experimental verification confirmed that the FAM234B expression was significantly higher at the mRNA and protein levels in luminal BC tissues than in adjacent normal tissues. High FAM234B expression was significantly correlated with older age, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor 2-negative, wild-type p53, low Nottingham prognostic index, low Scarff-Bloom-Richardson grade, lymph node metastasis positivity, and high tumor stage. Moreover, survival analysis indicated that high FAM234B expression was significantly related to a worse prognosis in patients with luminal BC. GSEA indicated that FAM234B was positively related to membrane transport process and negatively associated with immune response function. Besides, mechanism exploration indicated that pseudogene HTR7P1 might act as endogenous RNA to compete with has-miR-1271-5p or has-miR-381-3p for binding to FAM234B, thereby upregulating the expression of FAM234B in luminal BC. Conclusion Our results suggest that FAM234B may be a candidate therapeutic target or prognostic marker for luminal breast cancer.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3′ boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5′ splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP.

Intron-targeted gene insertion strategy using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated Cas9) has been shown to be a potential tool for crop genetic improvement by targeted mutagenesis or gene replacement of an elite allele into widely cultivated rice varieties. The rice blast resistant protein Pi-ta, differs from its susceptible counterpart, pi-ta, by a single amino acid in exon 2. To create new materials resistant to the rice blast disease, we inserted a genomic fragment containing the exon 2 and 3′ untranslated region (3′ UTR) of Pi-ta into intron 1 of pi-ta in rice materials susceptible to rice blast using the intron-targeted insertion strategy. The gene insertion frequency was 3.8%. Several novel transgene-free progeny with stably inherited homozygous insert were identified in the T1 generation, which have been crossed to rice germplasm bearing other resistance gene (R gene) for pyramiding of R genes. This work verified the feasibility of using the genome editing technology in improvement of qualitative agronomic trait in crops.

Pangolins are among the most critically endangered animals due to heavy poaching and worldwide trafficking. However, their demographic histories and the genomic consequences of their recent population declines remain unknown. We generated high-quality de novo reference genomes for critically endangered Malayan (Manis javanica, MJ) and Chinese (M. pentadactyla, MP) pangolins and re-sequencing population genomic data from 74 MJs and 23 MPs. We recovered the population identities of illegally traded pangolins and previously unrecognized genetic populations that should be protected as evolutionarily distinct conservation units. Demographic reconstruction suggested environmental changes have resulted in a population size fluctuation of pangolins. Additionally, recent population size declines due to human activities have resulted in an increase in inbreeding and genetic load. Deleterious mutations were enriched in genes related to cancer/diseases and cholesterol homeostasis, which may have increased their susceptibility to diseases and decreased their survival potential to adapt to environmental changes and high-cholesterol diets. This comprehensive study provides not only high-quality pangolin reference genomes, but also valuable information concerning the driving factors of long-term population size fluctuations and the genomic impact of recent population size declines due to human activities, which is essential for pangolin conservation management and global action planning.

Background Thymidylate synthase (TYMS) polymorphisms are reported to be related to susceptibility to some cancers. However, no study exists on TYMS polymorphisms and glioma risk. This study aimed to evaluate the relationship between two common TYMS gene variants (rs1059394 C>T, rs2847153 G>A) and glioma susceptibility. Methods This case-control study included 605 patients and 1300 cancer-free individuals. Genotyping was performed using Sequenom Mass-ARRAY. We determined odds ratios (ORs) and their 95% confidence intervals (CIs) to estimate the correlations. Results The analysis revealed that rs1059394 TT and CT+TT genotype had significantly low glioma risk (TT to CC: OR = 0.71, 95% CI = 0.52-0.97, P = 0.03; CT+TT to CC: OR = 0.74, 95% CI = 0.55-0.99, P = 0.04). However, no significant difference was found between rs2847153 and glioma risk in any genetic model (P﹥0.05). In high-grade gliomas, the GA and GA+AA genotypes of rs2847153 made the majority of genotypes, compared with GG genotype (GA to GG: OR = 2.01, 95% CI = 1.39-2.91, P < 0.001; GA+AA to GG: OR = 1.78, 95% CI =1.25-2.54, P < 0.001). Moreover, online expression quantitative trait locus (eQTL) analysis indicated that these two polymorphisms may alter TYMS gene expression in transformed fibroblast cells. Conclusion Our study provides evidence of the effect of TYMS rs1059394 on the susceptibility of glioma. In high-grade gliomas, compared with GG genotype, the GA and GA+AA genotypes of rs2847153 comprise a larger proportion.

Long noncoding RNA (lncRNA) polymorphisms are reportedly in connection with tumor susceptibility and prognosis. Glioma is one of the most aggressive and common cancers of the central nervous system. This study aimed to investigate the relationship between four lncRNA variants and glioma susceptibility and prognosis in a Chinese Han population. Sequenom Mass-ARRAY was used to genotype 605 patients with glioma and 1300 cancer-free individuals. Odds ratios or hazard ratios and related 95% confidence intervals were calculated to estimate the correlations. Logistic and Cox regression models, log-rank tests, and Kaplan-Meier curves were used for the statistical analysis. Six inheritance models showed that ANRIL rs2151280 variant genotype (A>G) was related to the susceptibility of glioma, while the other three lncRNAs showed no association. Patients treated with temozolomide or nimustine had better progression-free survival (PFS) and overall survival (OS) than those treated with platinum. Besides, patients aged older than 40 years showed a poorer OS. The Cox multivariate analysis revealed that the rs1136410 GG genotype (A>G) was beneficial for OS and PFS. The Kaplan-Meier analyses indicated that rs1136410 A>G and the rs7763881 A>C were associated with longer OS. ANRIL rs2151280 variant genotype might increase susceptibility of glioma. In addition, PARP1 rs1136410 variant genotype could be beneficial for the overall survival of patients with glioma. More research data are needed to further validate our results.

Hotspot p53 mutants augment cancer cell proliferation, metastasis and metabolism through their gain-of-function (GOF). Ovarian cancer sustains the highest frequency of TP53 mutations, but the mechanisms underlying regulation of mutant p53s’ GOF in this type of cancer remain incompletely understood. Herein, we identified the E3-ubiquitin ligase TRIM71 as a novel mutant p53-binding protein. Ectopic TRIM71-induced ubiquitination and proteasomal degradation of mutant p53 by binding to its transactivation (TA) domain, and inhibited the expression of a broad spectrum of mutant p53 target genes. Ectopic TRIM71 also restrained, whereas ablation of TRIM71 endorsed, ovarian carcinoma cell growth in vitro and in vivo. Significantly, TRIM71 overexpression is highly associated with favorable prognosis, particularly, in TP53-mutated ovarian carcinomas. Altogether, our findings unveil the anti-tumor function of TRIM71 in ovarian cancer development and prognosis by downregulating mutant p53s.

Single-cell RNA (scRNA) profiling or scRNA-sequencing (scRNA-seq) makes it possible to parallelly investigate diverse molecular features of multiple types of cells in a given plant tissue and discover cell developmental processes. In this study, we evaluated the effects of sample size (i.e., cell number) on the outcome of single-cell transcriptome analysis by sampling different numbers of cells from a pool of ~57,000 Arabidopsis thaliana root cells integrated from five published studies. Our results indicated that the most significant principal components could be achieved when 20,000–30,000 cells were sampled, a relatively high reliability of cell clustering could be achieved by using ~20,000 cells with little further improvement by using more cells, 96% of the differentially expressed genes could be successfully identified with no more than 20,000 cells, and a relatively stable pseudotime could be estimated in the subsample with 5000 cells. Finally, our results provide a general guide for optimizing sample size to be used in plant scRNA-seq studies.

The RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) was recently shown to play a role in cancer development. However, the function and mechanism of RMRP during cancer progression remain incompletely understood. Here, we report that RMRP is amplified and highly expressed in various malignant cancers, and the high level of RMRP is significantly associated with their poor prognosis, including breast cancer. Consistent with this, ectopic RMRP promotes proliferation and migration ofTP53-mutated breast cancer cells, whereas depletion of RMRP leads to inhibition of their proliferation and migration. RNA-seq analysis reveals AKT as a downstream target of RMRP. Interestingly, RMRP indirectly elevates AKT expression by preventing AKT mRNA from miR-206-mediated targeting via a competitive sequestering mechanism. Remarkably, RMRP endorses breast cancer progression in an AKT-dependent fashion, as knockdown of AKT completely abolishes RMRP-induced cancer cell growth and migration. Altogether, our results unveil a novel role of the RMRP-miR-206-AKT axis in breast cancer development, providing a potential new target for developing an anti-breast cancer therapy.

Recombination is a major force that shapes genetic diversity. Determination of recombination rate is important and can theoretically be improved by increasing the sample size. However, it is nearly impossible to estimate recombination rates using traditional population genetics methods when the sample size is large because these methods are highly computationally demanding. In this study, we used a refined machine learning approach to estimate the recombination rate of the human genome using the UK10K human genomic dataset with 7,562 genomic sequences and its three subsets with 200, 400 and 2,000 genomic sequences. The estimation was performed under the human Out-of-Africa demographic model. We not only obtained an accurate human genetic map, but also found that the fluctuation of estimated recombination rate is reduced along the human genome when the sample size increases. The estimated UK10K recombination rate heterogeneity is less than that estimated from its subsets. Our results demonstrate how the sample size affects the estimated recombination rate, and analyses of a larger number of genomes result in a more precise estimation of recombination rate. The accurate genetic map based on UK10K data set is also expected to benefit other human biology researches.

Background High‐grade serous ovarian carcinoma (HGSOC) is the most common and aggressive histotype of epithelial ovarian cancer. The heterogeneity and molecular basis of this disease remain incompletely understood. Methods To address this question, we have performed a single‐cell transcriptomics analysis of matched primary and metastatic HGSOC samples. Results A total of 13 571 cells are categorized into six distinct cell types, including epithelial cells, fibroblast cells, T cells, B cells, macrophages, and endothelial cells. A subset of aggressive epithelial cells with hyperproliferative and drug‐resistant potentials is identified. Several new markers that are highly expressed in epithelial cells are characterized, and their roles in ovarian cancer cell growth and migration are further confirmed. Dysregulation of multiple signaling pathways, including the translational machinery, is associated with ovarian cancer metastasis through the trajectory analysis. Moreover, single‐cell regulatory network inference and clustering (SCENIC) analysis reveals the gene regulatory networks and suggests the JUN signaling pathway as a potential therapeutic target for treatment of ovarian cancer, which is validated using the JUN/AP‐1 inhibitor T‐5224. Finally, our study depicts the epithelial‐fibroblast cell communication atlas and identifies several important receptor‐ligand complexes in ovarian cancer development. Conclusions This study uncovers new molecular features and the potential therapeutic target of HGSOC, which would advance the understanding and treatment of the disease., (1) Single‐cell transcriptomics analysis of HGSOC samples reveals six distinct cell types. (2) Characterization of epithelial cell subclusters identifies novel markers for HGSOC. (3) Subclustering fibroblast cells suggests their functional heterogeneity. (4) Our study also uncovers the JUN pathway and several ligand‐receptor signals as potential drivers for HGSOC.

Significance The tumor suppressor p53 prevents tumorigenesis, while inactivation of p53 promotes cancer development and drug resistance. Here, we identify that a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), promotes growth and proliferation of colorectal cancer cells by inhibiting p53 activity. Mechanistically, RMRP retains SNRPA1 in the nucleus, thus preventing its lysosomal degradation. The nuclear SNRPA1 then prompts MDM2-mediated p53 ubiquitination and degradation. Remarkably, RMRP expression is induced by poly (ADP-ribose) polymerase (PARP) inhibitors, a group of targeted anticancer drugs, through the transcription factor C/EBPβ. Targeting RMRP significantly enhances sensitivity of colorectal cancer cells to PARP inhibition by reactivating p53. Our study provides a possible mechanism underling tumor resistance to PARP inhibitors., p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPβ, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer.

p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPβ, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer.

Verticillium wilt, caused by Verticillium dahliae, is one of the most damaging and widespread soil-borne cotton diseases. The molecular mechanisms underlying the cotton defense against V. dahliae remain largely elusive. Here, we compared the transcriptional differences between Upland cotton cultivars: one highly resistant (HR; Shidalukang 1) and one highly susceptible (HS; Junmian 1). This was done at multiple time points after V. dahliae inoculation, which identified 2010 and 1275 differentially expressed genes (DEGs) in HR and HS, respectively. Plant hormone signal transduction-related genes were enriched in HR, whereas genes related to lignin biosynthesis were enriched in both HR and HS. Weighted gene co-expression network analysis (WGCNA) using the 2868 non-redundant genes differentially expressed between the V. dahliae infected and uninfected samples in HR or HS identified 10 different gene network modules and 22 hub genes with a potential role in regulating cotton defense against V. dahliae infection. GhGDH2, encoding glutamate dehydrogenase (GDH), was selected for functional characterization. Suppressing the expression level of GhGDH2 by virus-induced gene silencing (VIGS) in HS led to inhibition of the salicylic acid (SA) biosynthesis/signaling pathways and activation of the jasmonic acid (JA) biosynthesis/signaling pathways, which resulted in an increase of 42.1% JA content and a reduction of 78.9% SA content in cotton roots, and consequently enhanced V. dahliae resistance. Our finding provides new insights on the molecular mechanisms of cotton resistance to V. dahliae infection and candidate genes for breeding V. dahliae resistance cotton cultivars by genetic modification.

SUMMARYThe demographic history is a foundation of human evolutionary studies. However, the ancient demographic history during the Mid-Pleistocene is poorly investigated while it is essential for understanding the early origin of humankind. Here we present the fast infinitesimal time coalescent (FitCoal) process, which allows the analytical calculation of the composite likelihood of a site frequency spectrum and provides the precise inference of demographic history. We apply it to analyze 3,154 present-day human genomic sequences. We find that African populations have passed through a population super bottleneck, a small effective size of approximately 1,280 breeding individuals between 930 and 813 thousand years ago. Further analyses confirm the existence of the super bottleneck on non-African populations although it cannot be directly inferred. This observation, together with simulation results, indicates that confounding factors, such as population structure and selection, are unlikely to affect the inference of the super bottleneck. The time interval of the super bottleneck coincides with a gap in the human fossil record in Africa and possibly marks the origin ofHomo heidelbergensis. Our results provide new insights into human evolution during the Mid-Pleistocene.

Black root rot (BRR) is an economically important disease of cotton and other crops, especially in cooler regions with short growing seasons. Symptoms include black discoloration of the roots, reduced number of lateral roots and stunted or slow plant growth. The cultivated tetraploid Gossypium species are susceptible to BRR. Resistance to BRR was identified in G. arboreum accession BM13H and is associated with reduced and restricted hyphal growth and less sporulation. Transcriptome analysis indicates that BM13H responds to infection at early time points 2- and 3-days post-inoculation, but by day 5, few differentially expressed genes are observed between infected and uninfected roots. Inheritance of BM13H resistance to BRR was evaluated in an F6 recombinant inbred population and shows a single semi-dominant locus conferring resistance that was fine mapped to a region on chromosome 1, containing ten genes including five putative resistance-like genes.

The study performed genome-wide identification, characterization and evolution analysis of gene clusters for phytoalexin terpenoid biosynthesis in tobacco, and specifically illustrated ones for capsidiol, an efficient defensive specialized metabolite. Terpenoid phytoalexins play an important role in plant self-defense against pest and pathogen attack. Terpenoid biosynthesis involves terpene synthase and cytochrome P450, which always locate and function as cluster(s). In this study, we performed genome-wide investigation of metabolic gene clusters involved in terpenoid production in tobacco (Nicotiana tabacum). Due to the complexity of the tobacco genome, we modified a published prediction pipeline to reduce the influence of the large number of repeats and to improve the annotation of tobacco genes with respect to their metabolic functions. We identified 1181 metabolic gene clusters with 34 of them potentially being involved in terpenoid biosynthesis. Through integration with transcriptome and metabolic pathway annotation analyses, 3 of the 34 terpenoid biosynthesis-related gene clusters were determined to be high-confidence ones, with 2 involved in biosynthesis of capsidiol, a terpenoid recognized as 1 of the effective resistance compounds in the Nicotiana species. The capsidiol-related gene cluster was conserved in N. sylvestris, N. tomentosiformis and N. attenuate. Our findings demonstrate that phytoalexins in tobacco can arise from operon-like gene clusters, a genomic pattern characterized as being beneficial for rapid stress response, gene co-regulation, co-function and co-heredity.

Summary Brassica napus (AACC, 2n = 38) is an important oilseed crop grown worldwide. However, little is known about the population evolution of this species, the genomic difference between its major genetic groups, such as European and Asian rapeseed, and the impacts of historical large‐scale introgression events on this young tetraploid. In this study, we reported the de novo assembly of the genome sequences of an Asian rapeseed (B. napus), Ningyou 7, and its four progenitors and compared these genomes with other available genomic data from diverse European and Asian cultivars. Our results showed that Asian rapeseed originally derived from European rapeseed but subsequently significantly diverged, with rapid genome differentiation after hybridization and intensive local selective breeding. The first historical introgression of B. rapa dramatically broadened the allelic pool but decreased the deleterious variations of Asian rapeseed. The second historical introgression of the double‐low traits of European rapeseed (canola) has reshaped Asian rapeseed into two groups (double‐low and double‐high), accompanied by an increase in genetic load in the double‐low group. This study demonstrates distinctive genomic footprints and deleterious SNP (single nucleotide polymorphism) variants for local adaptation by recent intra‐ and interspecies introgression events and provides novel insights for understanding the rapid genome evolution of a young allopolyploid crop.

Since wild-type p53 is central for maintaining genomic stability and preventing oncogenesis, its coding gene TP53 is highly mutated in ~50% of human cancers, and its activity is almost abrogated in the rest of cancers. Approximately 80% of p53 mutations are single point mutations with several hotspot mutations. Besides loss of function and dominant-negative effect on the wild-type p53 activity, the hotspot p53 mutants also acquire new oncogenic functions, so-called ‘gain-of-functions’ (GOF). Because the GOF of mutant p53 is highly associated with late-stage malignance and drug resistance, these p53 mutants have become hot targets for developing novel cancer therapies. In this essay, we review some recent progresses in better understanding of the role of mutant p53 GOF in chemoresistance and the underlying mechanisms, and discuss the pros and cons of targeting mutant p53 for the development of anti-cancer therapies.

Background Long noncoding RNAs (lncRNAs) are transcripts longer than 200 bp that do not encode proteins but nonetheless have been shown to play important roles in various biological processes in plants. Brassica napus is an important seed oil crop worldwide and the target of many genetic improvement activities. To understand better the function of lncRNAs in regulating plant metabolic activities, we carried out a genome-wide lncRNA identification of lncRNAs in Brassica napus with a focus on lncRNAs involved in lipid metabolism. Twenty ribosomal RNA depleted strand specific RNA-seq (ssRNA-seq) datasets were generatred using RNAs isolated from B. napus seeds at four developmental stages. For comparison we also included 30 publically available RNA-seq datasets generated from poly(A) enriched mRNAs isolated from from various Brassica napus tissues in our analysis. Results A total of 8905 lncRNA loci were identified, including 7100 long intergenic noncoding RNA (lincRNA) loci and 1805 loci generating long noncoding natural antisense transcript (lncNAT). Many lncRNAs were identified only in the ssRNA-seq and poly(A) RNA-seq dataset, suggesting that B. napus has a large lncRNA repertoire and it is necessary to use libraries prepared from different tissues and developmental stages as well as different library preparation approaches to capture the whole spectrum of lncRNAs. Analysis of coexpression networks revealed that among the regulatory modules are networks containing lncRNAs and protein-coding genes related to oil biosynthesis indicating a possible role of lncRNAs in the control of lipid metabolism. One such example is that several lncRNAs are potential regulators of BnaC08g11970D that encodes oleosin1, a protein found in oil bodies and involved in seed lipid accumulation. We also observed that the expression levels of B. napus lncRNAs is positively correlated with their conservation levels. Conclusions We demonstrated that the B. napus genome has a large number of lncRNA and that these lncRNAs are expressed broadly across many developmental times and in different tissue types. We also provide evidence indicating that specific lncRNAs appear to be important regulators of lipid biosynthesis forming regulatory networks with transcripts involved in lipid biosynthesis. We also provide evidence that these lncRNAs are conserved in other species of the Brassicaceae family. Electronic supplementary material The online version of this article (10.1186/s12864-018-5117-8) contains supplementary material, which is available to authorized users.

Summary Moderately rolled leaf is one of the target traits of the ideal plant architecture in rice breeding. Many genes, including homeodomain leucine zipper IV transcription factors ROC5 and ROC8, regulating rice leaf rolling have been cloned and functionally analysed. However, the molecular mechanism by which these genes modulate leaf‐rolling remains largely elusive. In this study, we demonstrated the transcription activation activity of both ROC8 and ROC5. Overexpressing ROC8 caused adaxially rolled leaves due to decreased number and size of bulliform cells, whereas knockout of ROC8 induced abaxially rolled leaves due to increased number and size of bulliform cells. ROC8 and ROC5 each could form homodimer, but ROC8 interacted preferably with ROC5 to forms a heterodimer. Importantly, we showed that the ROC8‐ROC5 heterodimer rather than the homodimer of ROC8 or ROC5 was functional as neither overexpressing ROC8 in the ROC5 mutant nor overexpressing ROC5 in the ROC8‐knockout line could rescue the mutant phenotype. This was further partially supported by the identification of a large number of common differentially expressed genes in single and double mutants of roc8 and roc5. ROC8 and ROC5 were functionally additive as the phenotype of abaxially rolled leaves was stronger in the roc5roc8 double mutant than in their single mutants. Our results provide evidence for the role of dimerization of ROC members in regulating leaf rolling of rice.

Use of naturally colored cotton (NCC) in the textile industry is limited due to its inferior fiber quality. Recent advances in understanding pigmentation in NCC fiber and the genetic relationship between pigmentation and fiber development may overcome this hindrance and can guide developing high fiber quality and yield NCC.

The function of 4-coumarate-CoA ligases (4CL) under abiotic stresses has been studied in plants, however, limited is known about the 4CL genes in cotton (G. hirsutum L.) and their roles in response to drought stress.We performed genome-wide identification of the 4CL genes in G. hirsutum and investigated the expression profiles of the identified genes in various cotton tissues and in response to stress conditions with an aim to identify 4CL gene(s) associated with drought tolerance. We identified 34 putative 4CL genes in G. hirsutum that were clustered into three classes. Genes of the same class usually share a similar gene structure and motif composition. Many cis-elements related to stress and phytohormone responses were found in the promoters of the Gh4CL genes. Of the 34 Gh4CL genes, 26 were induced by at least one abiotic stress and 10 (including Gh4CL7) were up-regulated under the polyethylene glycol (PEG) simulated drought stress conditions. Virus-induced gene silencing (VIGS) in cotton and overexpression (OE) in Arabidopsis thaliana were applied to investigate the biological function of Gh4CL7 in drought tolerance. The Gh4CL7-silencing cotton plants showed more sensitive to drought stress, probably due to decreased relative water content (RWC), chlorophyll content and antioxidative enzyme activity, increased stomatal aperture, and the contents of malondialdehyde (MDA) and hydrogen peroxide (HWe characterized the 4CL gene family in upland cotton and revealed a role of Gh4CL7 in lignin biosynthesis and drought tolerance.

The COVID-19 pandemic poses a great threat to human society. SARS-CoV-2 is mainly transmitted through social contact; however, it is highly debated whether cold-chain related transmission has occurred and can be identified in the epidemic areas of COVID-19. Here, we provide a new method and distinguish two transmission routes by detecting a lineage-specific reduction of SARS-CoV-2 mutation rate. After analyzing 1,610,125 SARS-CoV-2 genomic sequences, we find that two outbreaks in Xinfadi-Beijing and Auckland are cold-chain related and respectively caused by two mutation-dormant variants. A Dalian outbreak in July 2020 and a Yingkou outbreak ten months later are epidemiologically connected and derived from a cold-chain related variant. Mutation-dormant variants are detected during the spread of spike D614G variant and the Delta Variant of Concern. Cold-chain contaminations repeatedly caused by epidemiologically connected patients are also found and have resulted in infections. Moreover, the COVID-19 outbreak in Wuhan is likely to be cold-chain related. A systematic identification reveals that the frequency of cold-chain related transmission is in the order of magnitude of 0.1-10%. Our results indicate that that cold-chain related transmission is rare but happens globally.

COVID-19 has widely spread across the world, and much research is being conducted on the causative virus SARS-CoV-2. To help control the infection, we developed the Coronavirus GenBrowser (CGB) to monitor the pandemic. With CGB, 178,765 high quality SARS-CoV-2 genomic sequences were analyzed, and 121,522 mutations were identified. In total, 1,041 mutation cold spots were found, suggesting that these spots are key functional elements of SARS-CoV-2 and can be used for detection and vaccine development. CGB revealed 203 accelerated evolutions of SARS-CoV-2, but variants with accelerated evolution were not found to be highly contagious, suggesting that most of these evolutions are neutral. The B.1.1.7 (CGB75056.84017) lineage previously identified in the UK was not found to be significantly accelerated although its adaptive evolution was detected. Moreover, 2,297 strains with a significantly reduced evolutionary rate were identified, including three closely related variants widely spreading in Europe with no mutations in three months. By lineage tracing, a strain dated early March 2020 was determined to be the most recent common ancestor of nine strains collected from six different regions in three continents. This strain was also found to cause the outbreak in Xinfadi, Beijing, China in June 2020. CGB allows visualization and analysis of hundreds of thousands of SARS-CoV-2 genomic sequences. Distributed genome alignments and its effective analysis pipeline ensure timely update of the latest genomic data of SARS-CoV-2. CGB is an efficient platform for the general public to monitor the transmission and evolution of SARS-CoV-2.

Fear memory is a pivotal biological function by which organisms can predict possible danger to avoid or reduce harm. However, dysregulation of fear memory processing may lead to pathological fear or anxiety and produce serious clinical symptoms, such as post-traumatic stress disorder (PTSD). Iron deficiency (ID) is reported to inhibit the initiation of fear memory. In our study, we found that ferroportin1 (FPN1), the only known cellular iron export protein in mammals, and ablation in neurons and astrocytes caused iron deficiency in the cortex and hippocampus. However, little is known about its role in the development of fear memory. Moreover, direct evidence of the role of FPN1, or the related molecular mechanisms of such a role, in balancing brain iron homeostasis, especially in neuronal cells, is lacking. Herein, we deleted Fpn1 in mouse neurons, using Nestin-cre transgenic mice, and explored the impact on neuronal iron recycling and brain iron homeostasis in the cortex and hippocampus. We investigated the response of the mice to contextual fear and found that formation of fear memory was impeded after neuronal FPN1 depletion. We also found that FPN1 ablation in neurons and astrocytes caused an atypical expression of iron metabolism-related proteins in these two regions: decreased expression of DMT1, Ft-H, and Ft-L, and increased TfR1 expression. In addition, the decreased FPN1 in brain microvascular endothelial cells (BMVECs) also shed light on the cause of the decreased iron delivery to the brain through the blood-brain barrier (BBB). Our research highlights the major role played by FPN1 in brain iron homeostasis and identifies a potential target for the treatment of PTSD.

Anthocyanins are flavonoid pigments providing plants a range of colors from red, pink, orange to blue. Anthocyanins are synthesized in the cytosol but accumulate predominantly in the vacuoles through vacuolar sequestration involving glutathione S-transferases (GSTs) and multidrug and toxic compound extrusion (MATE) and the ATP binding cassette (ABC) transporters. However, little is known about anthocyanin-related GSTs in Upland cotton (Gossypium hirsutum L.). In this study, we performed genome-wide identification of GST genes in Upland cotton and identified GST genes functioning in accumulation of anthocyanins. We demonstrated that GhGSTF12 was able to complement the defective leaf color phenotypes of the Arabidopsis tt19 mutant caused by mutation in a GSTF gene. Virus-induced silencing of GhGSTF12 in the red leaf cultivar turned its red color to green and transient overexpression of GhGSTF12 accelerated anthocyanin accumulation in the red leaf cultivar but not in the green leaf cultivar. Collectively, GhGSTF12 may be involved in transport of anthocyanins from cytosol to vacuoles in cotton. These results also demonstrated a conserved function of plant GSTF genes in anthocyanin accumulation and provide a candidate gene for manipulating pigmentation in cotton tissues.

Climate change poses a considerable threat to the forest-steppe ecotone in arid mountain areas. However, it remains unclear how the forest-steppe ecotone responds to climate change due to the limitation of the traditional pollen assemblages, which greatly limits the understanding of the history of the forest-steppe ecotone. Here, we examined the Tien Mountains, the largest mountain system in the world&rsquo, s arid regions, as a case study to explore the migration of the forest-steppe ecotone using the pollen taxa diversity, by combining modern vegetation surveys, topsoil pollen and two fossil pollen sequences&mdash, in the mid-elevation forest belt (Sayram Lake) and in the low-elevation desert belt (Aibi Lake). We found that the forest-steppe migration followed Holocene climate change. Specifically, the forest belt where Picea schrenkiana Fisch. &amp, C.A.Mey. dominates has a very low pollen taxa diversity, characterized by high richness and low evenness, which plays a key role in mountainous diversity. By detecting the diversity change of the deposition sites, we found that in coping with the warm and wet middle Holocene, the forest belt expanded and widened as the observed diversities around the two lakes were very low, thus the forest-steppe ecotone moved downward accordingly. During the early and late Holocene, the forest belt and the forest-steppe ecotone moved upward under a warm and dry climate, and downward under a cold and wet climate, as there was a reduced forest belt effect on, or contribution to, the sites, and the observed diversities were high. Moisture loss may pose the greatest threat to the narrow forest-steppe ecotone, considering the climatic niche space and the limited living space for humidity-sensitive taxa. This study highlights that temperature and moisture co-influence the forest belt change, which further determines the position migration of the forest-steppe ecotone.

Main conclusion Long non-coding RNAs modulate gene activity in plant development and stress responses by various molecular mechanisms. Abstract Long non-coding RNAs (lncRNAs) are transcripts larger than 200 nucleotides without protein coding potential. Computational approaches have identified numerous lncRNAs in different plant species. Research in the past decade has unveiled that plant lncRNAs participate in a wide range of biological processes, including regulation of flowering time and morphogenesis of reproductive organs, as well as abiotic and biotic stress responses. LncRNAs execute their functions by interacting with DNA, RNA and protein molecules, and by modulating the expression level of their targets through epigenetic, transcriptional, post-transcriptional or translational regulation. In this review, we summarize characteristics of plant lncRNAs, discuss recent progress on understanding of lncRNA functions, and propose an experimental framework for functional characterization. Electronic supplementary material The online version of this article (10.1007/s00425-020-03480-5) contains supplementary material, which is available to authorized users.

We evaluated a two-component transposon iAc/Ds system for generating a library of insertional mutants in rice. The constructs used have gene or enhancer trapping properties, plasmid rescue and T-DNA/Ds launching pad reporter facilities. Mutagenic iAc/Ds lines were produced by three methods: crossing iAc and Ds containing lines; co-transformation with iAc and Ds constructs; and super-transformation of iAc transgenic calli with Ds constructs. First and second generation screening populations, derived from crosses (F2 and F3) or double transformation (DtT1 and DtT2), were analysed for stable insertion lines containing Ds transposed to locations unlinked to iAc. The average frequencies of putative stable insertion (PSI) lines in the F2, DtT1, F3 and DtT2 populations were 6.61, 5.58, 11.47 and 7.05% respectively, with large variations in these frequencies in screening populations derived from different mutagenic lines. Further analyses indicated that 41, 33, 65 and 64% of the PSI lines, respectively, have Ds transposed to locations unlinked to the original Ds launching pad. Using the plasmid rescue system, sequences flanking Ds from 137 PSI lines were obtained. Sixty-eight of these lines had unique insertions in genomic regions, of which 18 were known sequences. Because the average frequency of proven stable insertion lines in any of our screening populations has been less than 5%, we suggest that additional features should be incorporated in this two-component iAc/Ds system to increase the screening efficiency, and to make it suitable for large-scale insertional mutagenesis and determination of gene function in rice.

Background : Male sterility is an efficient trait for hybrid seed production and germplasm innovation. Until now, most studies on male sterility were on cytoplasmic and recessive genic sterility, with few on dominant genic male sterility, especially in cotton, due to lack of such mutant.Results : We discovered a natural male sterile (MS) Sea Island cotton ( G. barbadense ) mutant, Genetic analysis showed the mutation was caused by a dominant mutation in a single nuclear gene. Comparative cytological observation of anther sections from MS and WT uncovered cellular differences in anther at and after the tetrad stage of pollen mother cells (PMC). In the MS anthers, the outer wall of pollen grains was free of spinules, the tapetum was vacuolated and showed delayed degradation, consequently, no functional pollen grains. Comparison of transcriptomes from meiosis, tetrad, mononuclear and binuclear pollen, and pollen maturation stages identified 13,783 non-redundant differentially expressed genes (DEGs) between MS and WT. Based on the number of DEGs, analyses of enriched GO terms and KEGG pathways, it was evident that significant transcriptomic changes occurred at and after the tetrad stage, consistent with cytological observation, and that the major differences were on metabolism of starch, sucrose, ascorbate, aldarate, alanine, aspartate and glutamate, and biosynthesis of cutin, suberine and wax. WGCNA analysis identified five modules containing 920 genes highly related to anther development, especially the greenyellow module with 54 genes that was highly associated with PMC meiosis and tetrad formation. A NAC transcription factor ( Gh_D11G2469 ) was identified as a hub gene for this module, which warrants further functional characterization.Conclusions : We demonstrated that the MS trait was controlled by a single dominant nuclear gene and caused by delayed tapetum degradation at the tetrad stage. Comparative transcriptome analysis and gene network construction identified DEGs, enriched GO terms and metabolic pathways, and hub genes potentially associated with anther development and the MS trait, which will contribute to important ideas and basis of the experimental data related to the molecular mechanism of DGMS and the innovation of cotton germplasm resources.

The tumor suppressor p53 prevents tumorigenesis and cancer progression by maintaining genomic stability and inducing cell growth arrest and apoptosis. Because of the extremely detrimental nature of wild-type p53, cancer cells usually mutate the TP53 gene in favor of their survival and propagation. Some of the mutant p53 proteins not only lose the wild-type activity, but also acquire oncogenic function, namely “gain-of-function”, to promote cancer development. Growing evidence has revealed that various E3 ubiquitin ligases are able to target both wild-type and mutant p53 for degradation or inactivation, and thus play divergent roles leading to cancer cell survival or death in the context of different p53 status. In this essay, we reviewed the recent progress in our understanding of the p53-targeting E3 ubiquitin ligases, and discussed the potential clinical implications of these E3 ubiquitin ligases in cancer therapy.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP). Herein we used whole-exome sequencing to screen possible novel RPGR mutations in RP patients, and identified a novel missense mutation E585K in a patient with early onset but slow disease progression, and a frameshift deletion E998Gfs*78 in a patient with RP sine pigmento and high myopia. Intriguingly, bioinformatic analysis indicated that E585K probably affected RPGR RNA splicing instead of the protein sequence directly. Mini-gene assays in 293T cells revealed that splicing events of the E585K mutant were found to be also exist in wildtype, but with a shifted pattern. In the E585K mini-gene usage of an upstream alternative 5′ splice site (5′ ss) of exon 14 was enhanced, and other splicing events were suppressed, including the canonical 5′ ss of exon 14, skipping of exon 14/15 and retention of intron 14. As a result, RPGR splicing products of the E585K mini-gene were predominated by transcripts containing a 4-bp deletion, with a small fraction of in-frame transcripts containing a retended intron 14, which might explain the slow disease progression in the patient carrying the mutation. RNA-Seq analysis further confirmed existence of these splicing events in endogenous RPGR RNA in human retina, pointing to compromised splicing diversity in the E585K mutant. Our findings thus added to the understanding of genotype-phenotype correlation in RP, and suggested that compromised RPGR splicing diversity might play a role in molecular mechanism of the disease.