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Simple Summary: RNA pseudouridine modifications are present in various RNAs across different organisms and play crucial roles in regulating gene expression during biological processes. The accurate identification of pseudouridine sites within RNA sequences is essential for understanding their functional mechanisms. This study proposes a novel ensemble learning predictor named PseUpred-ELPSO, which accurately predicts RNA pseudouridine sites. The predictor demonstrates excellent performance in both cross-validation and independent testing. A user-friendly web server has been established, making it a powerful tool for pseudouridine site identification. RNA pseudouridine modification exists in different RNA types of many species, and it has a significant role in regulating the expression of biological processes. To understand the functional mechanisms for RNA pseudouridine sites, the accurate identification of pseudouridine sites in RNA sequences is essential. Although several fast and inexpensive computational methods have been proposed, the challenge of improving recognition accuracy and generalization still exists. This study proposed a novel ensemble predictor called PseUpred-ELPSO for improved RNA pseudouridine site prediction. After analyzing the nucleotide composition preferences between RNA pseudouridine site sequences, two feature representations were determined and fed into the stacking ensemble framework. Then, using five tree-based machine learning classifiers as base classifiers, 30-dimensional RNA profiles are constructed to represent RNA sequences, and using the PSO algorithm, the weights of the RNA profiles were searched to further enhance the representation. A logistic regression classifier was used as a meta-classifier to complete the final predictions. Compared to the most advanced predictors, the performance of PseUpred-ELPSO is superior in both cross-validation and the independent test. Based on the PseUpred-ELPSO predictor, a free and easy-to-operate web server has been established, which will be a powerful tool for pseudouridine site identification. [ABSTRACT FROM AUTHOR]

Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is a RNA helicase required for the translation of 5’ structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5’ structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity. [ABSTRACT FROM AUTHOR]

The pine aphid Cinara pinitabulaeformis Zhang et Zhang is the main pine pest in China, it causes pine needles to produce dense dew (honeydew) which can lead to sooty mold (black filamentous saprophytic ascomycetes). Although common chemical and physical strategies are used to prevent the disease caused by C. pinitabulaeformis Zhang et Zhang, new strategies based on biological and/or genetic approaches are promising to control and eradicate the disease. However, there is no information about genomics, proteomics or transcriptomics to allow the design of new control strategies for this pine aphid. We used next generation sequencing technology to sequence the transcriptome of C. pinitabulaeformis Zhang et Zhang and built a transcriptome database. We identified 80,259 unigenes assigned for Gene Ontology (GO) terms and information for a total of 11,609 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs). A total of 10,806 annotated unigenes were analyzed to identify the represented biological pathways, among them 8,845 unigenes matched with 228 KEGG pathways. In addition, our data describe propagative viruses, nutrition-related genes, detoxification related molecules, olfactory related receptors, stressed-related protein, putative insecticide resistance genes and possible insecticide targets. Moreover, this study provides valuable information about putative insecticide resistance related genes and for the design of new genetic/biological based strategies to manage and control C. pinitabulaeformis Zhang et Zhang populations. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma. [ABSTRACT FROM AUTHOR]

Recent studies indicate that soluble β-amyloid (sAβ) oligomers, rather than their fibrillar aggregates, contribute to the pathogenesis of Alzheimer's disease (AD), though the mechanisms of their neurotoxicity are still elusive. Here, we demonstrate that sAβ derived from 7PA2 cells exert a much stronger effect on the regulation of a set of functionally validated microRNAs (miRNAs) in primary cultured neurons than the synthetic insoluble Aβ fibrils (fAβ). Synthetic sAβ peptides at a higher concentration present comparable effect on these miRNAs in our neuronal model. Further, the sAβ-induced miR-134, miR-145 and miR-210 expressions are fully reversed by two selective N-methyl-d-aspartate (NMDA) receptor inhibitors, but are neither reversed by insulin nor by forskolin, suggesting an NMDA receptor-dependent, rather than PI3K/AKT or PKA/CREB signaling dependent regulatory mechanism. In addition, the repression of miR-107 expression by the sAβ containing 7PA2 CM is likely involved multiple mechanisms and multiple players including NMDA receptor, N-terminally truncated Aβ and reactive oxygen species (ROS). [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The disease is characterized by various cytogenetic and molecular abnormalities with distinct prognoses and gene expression profiles. Emerging evidence has suggested that circulating microRNAs (miRNAs) could serve as noninvasive biomarkers for cancer detection; however, little is known about circulating miRNA profiles in AML patients. In this study, a genome-wide serum miRNA expression analysis was performed using Solexa sequencing for initial screen, followed by validation with real-time PCR assays. The analysis was conducted on training and verification sets of serum samples from 140 newly diagnosed AML patients and 135 normal adult donors. After a two-phase selection and validation process, 6 miRNAs, miR-10a-5p, miR-93-5p, miR-129-5p, miR-155-5p, miR-181b-5p and miR-320d, were found to have significantly different expression levels in AML compared with control serum samples. Furthermore, unsupervised clustering analysis revealed the remarkable ability of the 6-miRNA profile to differentiate between AML patients and normal controls. The areas under the ROC curve for the selected miRNAs ranged from 0.8129 to 0.9531. More importantly, miR-181b-5p levels in serum were significantly associated with overall survival. These data demonstrated that the expression patterns of circulating miRNAs were systematically altered in AML and miR-181b-5p may serve as a predictor for overall survival in AML patients. [ABSTRACT FROM AUTHOR]

Purpose: Dysregulation of microRNA (miRNA) metabolism has been observed in a variety of human cancers, but the expression patterns of the enzymes responsible for generating miRNAs remain largely unexplored. In this study, we investigated the expression profiles of the two most important enzymes of the miRNA machinery, Drosha and Dicer, which were closely correlated with nasopharyngeal carcinoma (NPC) and patient survival. Methods: Dicer and Drosha mRNA levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) using 24 NPC tissues, 7 normal nasopharyngeal epithelium samples (NPE) and NPC cell lines. In addition, protein levels were detected by immunohistochemistry (IHC) using an NPC tissue microarray (TMA), which include 251 NPC and 105 NPE cases. For some NPC patients can not be contacted, the survival data were available only for 146 patients. Kaplan-Meier analysis was performed, and the chi-square and log-rank tests were used to detect significance levels using SPSS 15.0 software. Results: The mean level of Dicer and Drosha mRNA were significantly down-regulated in NPC tissue specimens and cell lines when compared with controls. The low levels of Dicer and Drosha protein were frequently seen in NPC, and the low expression of Dicer and Drosha protein was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) of NPC patients. Conclusions: We observed that Drosha and Dicer expression was dysregulation in NPC compared with healthy control samples and was significantly correlated with shorter PFS and OS of NPC patients. Therefore, we hypothesise that the expression levels of Dicer and Drosha could be used as potential prognostic biomarkers for NPC. [ABSTRACT FROM AUTHOR]