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Background: Extracellular vesicles (EVs) and non-coding RNAs (ncRNAs) are emerging contributors to Alzheimer's disease (AD) pathophysiology. Differential abundance of ncRNAs carried by EVs may provide valuable insights into underlying disease mechanisms. Brain tissue-derived EVs (bdEVs) are particularly relevant, as they may offer valuable insights about the tissue of origin. However, there is limited research on diverse ncRNA species in bdEVs in AD. Objective: This study explored whether the non-coding RNA composition of EVs isolated from post-mortem brain tissue is related to AD pathogenesis. Methods: bdEVs from age-matched late-stage AD patients (n = 23) and controls (n = 10) that had been separated and characterized in our previous study were used for RNA extraction, small RNA sequencing, and qPCR verification. Results: Significant differences of non-coding RNAs between AD and controls were found, especially for miRNAs and tRNAs. AD pathology-related miRNA and tRNA differences of bdEVs partially matched expression differences in source brain tissues. AD pathology had a more prominent association than biological sex with bdEV miRNA and tRNA components in late-stage AD brains. Conclusions: Our study provides further evidence that EV non-coding RNAs from human brain tissue, including but not limited to miRNAs, may be altered and contribute to AD pathogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: The protein translation machinery, of which tRNA is an essential part, is critical in controlling the growth of tumor cells. The development of cancer is also influenced by translational dysregulation. Understanding the rewiring of gene expression at the translational level, which underpins the development of transformational phenotypes during cancer, has made tremendous strides in recent years. We have found that the mode of translation regulation centered on tRNAs affects the translation system in various cancer types in a variety of different ways. In addition to the expression level of tRNA itself, codon and amino acid usage bias, tRNA modification regulation, and tRNA-derived fragments all play important roles. This review discusses recent developments and new insights to elucidate the role of tRNA-centered translational regulatory models in some aspects of carcinogenic and cancer cell activity. Cancer is a leading cause of morbidity and mortality worldwide. While numerous factors have been identified as contributing to the development of malignancy, our understanding of the mechanisms involved remains limited. Early cancer detection and the development of effective treatments are therefore critical areas of research. One class of molecules that play a crucial role in the transmission of genetic information are transfer RNAs (tRNAs), which are the most abundant RNA molecules in the human transcriptome. Dysregulated synthesis of tRNAs directly results in translation disorders and diseases, including cancer. Moreover, various types of tRNA modifications and the enzymes responsible for these modifications have been implicated in tumor biology. Furthermore, alterations in tRNA modification can impact tRNA stability, and impaired stability can prompt the cleavage of tRNAs into smaller fragments known as tRNA fragments (tRFs). Initially believed to be random byproducts lacking any physiological function, tRFs have now been redefined as non-coding RNA molecules with distinct roles in regulating RNA stability, translation, target gene expression, and other biological processes. In this review, we present recent findings on translational regulatory models centered around tRNAs in tumors, providing a deeper understanding of tumorigenesis and suggesting new directions for cancer treatment. [ABSTRACT FROM AUTHOR]

BackgroundEukaryotes acquired the trait of oxygenic photosynthesis through endosymbiosis of the cyanobacterial progenitor of plastid organelles. Despite recent advances in the phylogenomics of Cyanobacteria, the phylogenetic root of plastids remains controversial. Although a single origin of plastids by endosymbiosis is broadly supported, recent phylogenomic studies are contradictory on whether plastids branch early or late within Cyanobacteria. One underlying cause may be poor fit of evolutionary models to complex phylogenomic data.ResultsUsing Posterior Predictive Analysis, we show that recently applied evolutionary models poorly fit three phylogenomic datasets curated from cyanobacteria and plastid genomes because of heterogeneities in both substitution processes across sites and of compositions across lineages. To circumvent these sources of bias, we developed CYANO-MLP, a machine learning algorithm that consistently and accurately phylogenetically classifies ("phyloclassifies") cyanobacterial genomes to their clade of origin based on bioinformatically predicted function-informative features in tRNA gene complements. Classification of cyanobacterial genomes with CYANO-MLP is accurate and robust to deletion of clades, unbalanced sampling, and compositional heterogeneity in input tRNA data. CYANO-MLP consistently classifies plastid genomes into a late-branching cyanobacterial sub-clade containing single-cell, starch-producing, nitrogen-fixing ecotypes, consistent with metabolic and gene transfer data.ConclusionsPhylogenomic data of cyanobacteria and plastids exhibit both site-process heterogeneities and compositional heterogeneities across lineages. These aspects of the data require careful modeling to avoid bias in phylogenomic estimation. Furthermore, we show that amino acid recoding strategies may be insufficient to mitigate bias from compositional heterogeneities. However, the combination of our novel tRNA-specific strategy with machine learning in CYANO-MLP appears robust to these sources of bias with high accuracy in phyloclassification of cyanobacterial genomes. CYANO-MLP consistently classifies plastids as late-branching Cyanobacteria, consistent with independent evidence from signature-based approaches and some previous phylogenetic studies.

Abstract Transfer RNAs (tRNAs) promote protein translation by binding to the corresponding amino acids and transporting them to the ribosome, which is essential in protein translation. tRNA-derived small RNAs (tsRNAs) are derived fragments of tRNAs that are cleaved explicitly under certain conditions. An increasing amount of research has demonstrated that tsRNAs have biological functions rather than just being degradation products. tsRNAs can exert functions such as regulating gene expression to influence cancer progression. Their dysregulation is closely associated with various cancers and can serve as diagnostic and prognostic biomarkers for cancer. This review summarizes the generation, classification, and biological functions of tsRNAs, and highlights the roles of tsRNAs in different cancers and their applications as tumor markers.

Simple Summary: Cichlids are a unique example of fish diversity and species richness which have been explained by sympatric speciation at different freshwater sources in Africa. The mitochondria contribute to cell vitality by providing energy. It contains a circular genome with an established translation system that is spatially independent of the cytosolic counterpart. The current study aimed to investigate the evolutionary dynamics of the mitochondrial tRNA and its role in cichlids' diversity. The available cichlid mitogenomes in the public database were filtered, in addition to newly sequenced accessions from a specific cichlid group known as the haplotilapiine lineage that is widely distributed in the Egyptian sector of the Nile River. Based on the comparative analysis of mitogenomic data, we identified 22 tRNA genes, in which a single gene was D-armless, while the cloverleaf secondary structure subdivided into stem-loop formations was predicted and used to define the levels of genetic divergence for the remained tRNAs. Peculiarly, in cichlids, the formation known as "T-arm" showed the lowest polymorphism levels among other structures in contrast to other organisms (e.g., scorpions). Comparing the whole family to the specific haplotilapiine lineage showed that the tryptophan tRNA was the most conserved tRNA, with signatures of possible purifying selection. The mitochondrial transfer RNA genes (tRNAs) attract more attention due to their highly dynamic and rapidly evolving nature. The current study aimed to detect and evaluate the dynamics, characteristic patterns, and variations of mitochondrial tRNAs. The study was conducted in two main parts: first, the published mitogenomic sequences of cichlids mt tRNAs have been filtered. Second, the filtered mitochondrial tRNA and additional new mitogenomes representing the most prevalent Egyptian tilapiine were compared and analyzed. Our results revealed that all 22 tRNAs of cichlids folded into a classical cloverleaf secondary structure with four domains, except for trnSGCU, missing the D domain in all cichlids. When consensus tRNAs were compared, most of the mutations were observed in the trnP at nucleotide levels (substitutions and indels), in contrast to trnLUAA. From a structural perspective, the anticodon loop and T-loop formations were the most conserved structures among all parts of the tRNA in contrast to the A-stem and D-loop formations. The trnW was the lowest polymorphic unneutral tRNA among all cichlids (both the family and the haplotilapiine lineage), in contrast with the neutral trnD that was extremely polymorphic among and within the haplotilapiine lineage species compared to other cichlids species. From a phylogenetic perspective, the trnC was extremely hypervariable and neutral tRNA in both haplotilapiine lineage and cichlids but was unable to report correct phylogenetic signal for the cichlids. In contrast to trnI and trnY, less variable neutral tRNAs that were able to cluster the haplotilapiine lineage and cichlids species as previously reported. By observing the DNA polymorphism in the coding DNA sequences (CDS), the highest affected amino acid by non-synonymous mutations was isoleucine and was equally mutated to valine and vice versa; no correlation between mutations in CDS and tRNAs was statistically found. The current study provides an insight into the mitochondrial tRNA evolution and its effect on the cichlid diversity and speciation model at the maternal level. [ABSTRACT FROM AUTHOR]

Noncoding RNAs (ncRNAs) constitute a class of nucleic acid molecules within cells that do not encode proteins but play important roles in regulating gene expression, maintaining cellular homeostasis, and mediating cell signaling. This class encompasses microRNAs (miRNAs), long noncoding RNAs (lncRNAs), transfer RNAs (tRNAs), circular RNAs (circRNAs), small interfering RNAs (siRNAs), and others. miRNAs are pivotal in the regulation of gene expression in hematologic malignancies. Aberrant expression of lncRNAs has been confirmed in cancerous tissues, implicating their involvement in carcinogenesis or tumor suppression processes. tRNAs may induce errors or disturbances in protein synthesis, thereby affecting normal cellular function and proliferation. Moreover, circRNAs influence disease progression in tumors by modulating the expression of relevant genes, and siRNAs can inhibit tumor cell proliferation, invasion, and metastasis while inducing apoptosis. This review will elucidate the biological functions of ncRNAs in multiple myeloma (MM) and explore their potential value as therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract The fundamental essence of life is based on process of interaction between nucleic acids and proteins. In a prebiotic world, amino acids, peptides, ions, and other metabolites acted in protobiotic routes at the same time on which RNAs performed catalysis and self-replication. Nevertheless, it was only when nucleic acids and peptides started to interact together in an organized process that life emerged. First, the ignition was sparked with the formation of a Peptidyl Transferase Center (PTC), possibly by concatenation of proto-tRNAs. This molecule that would become the catalytic site of ribosomes started a process of self-organization that gave origin to a protoorganism named FUCA, a ribonucleic ribosomal-like apparatus capable to polymerize amino acids. In that sense, we review hypotheses about the origin and early evolution of the genetic code. Next, populations of open biological systems named progenotes were capable of accumulating and exchanging genetic material, producing the first genomes. Progenotes then evolved in two paths: some presented their own ribosomes and others used available ribosomes in the medium to translate their encoded information. At some point, two different types of organisms emerged from populations of progenotes: the ribosome-encoding organisms (cells) and the capsid-encoding organisms (viruses).

Transfer RNAs (tRNAs) promote protein translation by binding to the corresponding amino acids and transporting them to the ribosome, which is essential in protein translation. tRNA-derived small RNAs (tsRNAs) are derived fragments of tRNAs that are cleaved explicitly under certain conditions. An increasing amount of research has demonstrated that tsRNAs have biological functions rather than just being degradation products. tsRNAs can exert functions such as regulating gene expression to influence cancer progression. Their dysregulation is closely associated with various cancers and can serve as diagnostic and prognostic biomarkers for cancer. This review summarizes the generation, classification, and biological functions of tsRNAs, and highlights the roles of tsRNAs in different cancers and their applications as tumor markers. [ABSTRACT FROM AUTHOR]

Infectious diseases pose two main compelling issues. First, the identification of the molecular factors that allow chronic infections, that is, the often completely asymptomatic coexistence of infectious agents with the human host. Second, the definition of the mechanisms that allow the switch from pathogen dormancy to pathologic (re)activation. Furthering previous studies, the present study (1) analyzed the frequency of occurrence of synonymous codons in coding DNA, that is, codon usage, as a genetic tool that rules protein expression; (2) described how human codon usage can inhibit protein expression of infectious agents during latency, so that pathogen genes the codon usage of which does not conform to the human codon usage cannot be translated; and (3) framed human codon usage among the front-line instruments of the innate immunity against infections. In parallel, it was shown that, while genetics can account for the molecular basis of pathogen latency, the changes of the quantitative relationship between codon frequencies and isoaccepting tRNAs during cell proliferation offer a biochemical mechanism that explains the pathogen switching to (re)activation. Immunologically, this study warns that using codon optimization methodologies can (re)activate, potentiate, and immortalize otherwise quiescent, asymptomatic pathogens, thus leading to uncontrollable pandemics.

Abstract Background For multicellular organisms, much remains unknown about the dynamics of synonymous codon and amino acid use in highly expressed genes, including whether their use varies with expression in different tissue types and sexes. Moreover, specific codons and amino acids may have translational functions in highly transcribed genes, that largely depend on their relationships to tRNA gene copies in the genome. However, these relationships and putative functions are poorly understood, particularly in multicellular systems. Results Here, we studied codon and amino acid use in highly expressed genes from reproductive and nervous system tissues (male and female gonad, somatic reproductive system, brain and ventral nerve cord, and male accessory glands) in the cricket Gryllus bimaculatus. We report an optimal codon, defined as the codon preferentially used in highly expressed genes, for each of the 18 amino acids with synonymous codons in this organism. The optimal codons were mostly shared among tissue types and both sexes. However, the frequency of optimal codons was highest in gonadal genes. Concordant with translational selection, a majority of the optimal codons had abundant matching tRNA gene copies in the genome, but sometimes obligately required wobble tRNAs. We suggest the latter may comprise a mechanism for slowing translation of abundant transcripts, particularly for cell-cycle genes. Non-optimal codons, defined as those least commonly used in highly transcribed genes, intriguingly often had abundant tRNAs, and had elevated use in a subset of genes with specialized functions (gametic and apoptosis genes), suggesting their use promotes the translational upregulation of particular mRNAs. In terms of amino acids, we found evidence suggesting that amino acid frequency, tRNA gene copy number, and amino acid biosynthetic costs (size/complexity) had all interdependently evolved in this insect model, potentially for translational optimization. Conclusions Collectively, the results suggest a model whereby codon use in highly expressed genes, including optimal, wobble, and non-optimal codons, and their tRNA abundances, as well as amino acid use, have been influenced by adaptation for various functional roles in translation within this cricket. The effects of expression in different tissue types and the two sexes are discussed.

The mitochondrial unfolded protein response (UPRmt) has emerged as a predominant mechanism that preserves mitochondrial function. Consequently, multiple pathways likely exist to modulate UPRmt. We discovered that the tRNA processing enzyme, homolog of ELAC2 (HOE-1), is key to UPRmt regulation in Caenorhabditis elegans. We find that nuclear HOE-1 is necessary and sufficient to robustly activate UPRmt. We show that HOE-1 acts via transcription factors ATFS-1 and DVE-1 that are crucial for UPRmt. Mechanistically, we show that HOE-1 likely mediates its effects via tRNAs, as blocking tRNA export prevents HOE-1-induced UPRmt. Interestingly, we find that HOE-1 does not act via the integrated stress response, which can be activated by uncharged tRNAs, pointing toward its reliance on a new mechanism. Finally, we show that the subcellular localization of HOE-1 is responsive to mitochondrial stress and is subject to negative regulation via ATFS-1. Together, we have discovered a novel RNA-based cellular pathway that modulates UPRmt.

Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. In addition to cleaving tRNA anticodon loops, ANG has been shown to cleave 3′-CCA termini of tRNAs in vitro, although it is not known whether this process occurs in cells. It has also been suggested that tiRNAs can be generated independently of ANG, although the role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we examined the involvement of ANG in stress-induced tRNA cleavage by focusing on its cleavage of CCA-termini as well as anticodon loops. We show that ANG is not responsible for CCA-deactivation under sodium arsenite (SA) treatment in cellulo, and although ANG treatment significantly increases 3′-tiRNA levels in cells, the majority of 3′-tiRNAs retain their 3′-CCA termini. Instead, other RNases can cleave CCA-termini in cells, although with low efficiency. Moreover, in the absence of ANG, other RNases are able to promote the production of tiRNAs in cells. Depletion of RNH1 (an endogenous inhibitor of RNase A superfamily) promotes constitutively-produced tiRNAs and CCA-deactivated tRNAs in cells. Interestingly, SA treatment in RNH1-depleted cells did not increase the amount of tiRNAs or CCA-deactivated tRNAs, suggesting that RNase A superfamily enzymes are largely responsible for SA-induced tRNA cleavage. We show that interplay between stress-induced RNases cause targeting tRNAs in a stress-specific manner in cellulo.

Bacteriophages (phages) are viruses that infect bacteria. They are the most abundant biological entity on Earth (current estimates suggest there to be perhaps 1031 particles) and are found nearly everywhere. Temperate phages can integrate into the chromosome of their host, and prophages have been found in abundance in sequenced bacterial genomes. Prophages may modulate the virulence of their host in different ways, e.g., by the secretion of phage-encoded toxins or by mediating bacterial infectivity. Some 70% of Streptococcus pneumoniae (the pneumococcus)—a frequent cause of otitis media, pneumonia, bacteremia and meningitis—isolates harbor one or more prophages. In the present study, over 4000 S. pneumoniae genomes were examined for the presence of prophages, and nearly 90% were found to contain at least one prophage, either defective (47%) or present in full (43%). More than 7000 complete putative integrases, either of the tyrosine (6243) or serine (957) families, and 1210 full-sized endolysins (among them 1180 enzymes corresponding to 318 amino acid-long N -acetylmuramoyl-L-alanine amidases [LytAPPH]) were found. Based on their integration site, 26 different pneumococcal prophage groups were documented. Prophages coding for tRNAs, putative virulence factors and different methyltransferases were also detected. The members of one group of diverse prophages (PPH090) were found to integrate into the 3' end of the host lytASpn gene encoding the major S. pneumoniae autolysin without disrupting it. The great similarity of the lytASpn and lytA PPH genes (85–92% identity) allowed them to recombine, via an apparent integrase-independent mechanism, to produce different DNA rearrangements within the pneumococcal chromosome. This study provides a complete dataset that can be used to further analyze pneumococcal prophages, their evolutionary relationships, and their role in the pathogenesis of pneumococcal disease. [ABSTRACT FROM AUTHOR]

Abstract Background Eukaryotes acquired the trait of oxygenic photosynthesis through endosymbiosis of the cyanobacterial progenitor of plastid organelles. Despite recent advances in the phylogenomics of Cyanobacteria, the phylogenetic root of plastids remains controversial. Although a single origin of plastids by endosymbiosis is broadly supported, recent phylogenomic studies are contradictory on whether plastids branch early or late within Cyanobacteria. One underlying cause may be poor fit of evolutionary models to complex phylogenomic data. Results Using Posterior Predictive Analysis, we show that recently applied evolutionary models poorly fit three phylogenomic datasets curated from cyanobacteria and plastid genomes because of heterogeneities in both substitution processes across sites and of compositions across lineages. To circumvent these sources of bias, we developed CYANO-MLP, a machine learning algorithm that consistently and accurately phylogenetically classifies (“phyloclassifies”) cyanobacterial genomes to their clade of origin based on bioinformatically predicted function-informative features in tRNA gene complements. Classification of cyanobacterial genomes with CYANO-MLP is accurate and robust to deletion of clades, unbalanced sampling, and compositional heterogeneity in input tRNA data. CYANO-MLP consistently classifies plastid genomes into a late-branching cyanobacterial sub-clade containing single-cell, starch-producing, nitrogen-fixing ecotypes, consistent with metabolic and gene transfer data. Conclusions Phylogenomic data of cyanobacteria and plastids exhibit both site-process heterogeneities and compositional heterogeneities across lineages. These aspects of the data require careful modeling to avoid bias in phylogenomic estimation. Furthermore, we show that amino acid recoding strategies may be insufficient to mitigate bias from compositional heterogeneities. However, the combination of our novel tRNA-specific strategy with machine learning in CYANO-MLP appears robust to these sources of bias with high accuracy in phyloclassification of cyanobacterial genomes. CYANO-MLP consistently classifies plastids as late-branching Cyanobacteria, consistent with independent evidence from signature-based approaches and some previous phylogenetic studies.

Bacteriophages (phages) are viruses that infect bacteria. They are the most abundant biological entity on Earth (current estimates suggest there to be perhaps 1031 particles) and are found nearly everywhere. Temperate phages can integrate into the chromosome of their host, and prophages have been found in abundance in sequenced bacterial genomes. Prophages may modulate the virulence of their host in different ways, e.g., by the secretion of phage-encoded toxins or by mediating bacterial infectivity. Some 70% of Streptococcus pneumoniae (the pneumococcus)—a frequent cause of otitis media, pneumonia, bacteremia and meningitis—isolates harbor one or more prophages. In the present study, over 4000 S. pneumoniae genomes were examined for the presence of prophages, and nearly 90% were found to contain at least one prophage, either defective (47%) or present in full (43%). More than 7000 complete putative integrases, either of the tyrosine (6243) or serine (957) families, and 1210 full-sized endolysins (among them 1180 enzymes corresponding to 318 amino acid-long N-acetylmuramoyl-L-alanine amidases [LytAPPH]) were found. Based on their integration site, 26 different pneumococcal prophage groups were documented. Prophages coding for tRNAs, putative virulence factors and different methyltransferases were also detected. The members of one group of diverse prophages (PPH090) were found to integrate into the 3’ end of the host lytASpn gene encoding the major S. pneumoniae autolysin without disrupting it. The great similarity of the lytASpnand lytAPPH genes (85–92% identity) allowed them to recombine, via an apparent integrase-independent mechanism, to produce different DNA rearrangements within the pneumococcal chromosome. This study provides a complete dataset that can be used to further analyze pneumococcal prophages, their evolutionary relationships, and their role in the pathogenesis of pneumococcal disease.

The mitochondrial transfer RNA genes (tRNAs) attract more attention due to their highly dynamic and rapidly evolving nature. The current study aimed to detect and evaluate the dynamics, characteristic patterns, and variations of mitochondrial tRNAs. The study was conducted in two main parts: first, the published mitogenomic sequences of cichlids mt tRNAs have been filtered. Second, the filtered mitochondrial tRNA and additional new mitogenomes representing the most prevalent Egyptian tilapiine were compared and analyzed. Our results revealed that all 22 tRNAs of cichlids folded into a classical cloverleaf secondary structure with four domains, except for trnSGCU, missing the D domain in all cichlids. When consensus tRNAs were compared, most of the mutations were observed in the trnP at nucleotide levels (substitutions and indels), in contrast to trnLUAA. From a structural perspective, the anticodon loop and T-loop formations were the most conserved structures among all parts of the tRNA in contrast to the A-stem and D-loop formations. The trnW was the lowest polymorphic unneutral tRNA among all cichlids (both the family and the haplotilapiine lineage), in contrast with the neutral trnD that was extremely polymorphic among and within the haplotilapiine lineage species compared to other cichlids species. From a phylogenetic perspective, the trnC was extremely hypervariable and neutral tRNA in both haplotilapiine lineage and cichlids but was unable to report correct phylogenetic signal for the cichlids. In contrast to trnI and trnY, less variable neutral tRNAs that were able to cluster the haplotilapiine lineage and cichlids species as previously reported. By observing the DNA polymorphism in the coding DNA sequences (CDS), the highest affected amino acid by non-synonymous mutations was isoleucine and was equally mutated to valine and vice versa; no correlation between mutations in CDS and tRNAs was statistically found. The current study provides an insight into the mitochondrial tRNA evolution and its effect on the cichlid diversity and speciation model at the maternal level.

In the past 2 decades, the discovery of a new class of small RNAs, known as tRNA-derived fragments (tRFs), shed light on a new layer of regulation implicated in many biological processes. tRFs originate from mature tRNAs and are classified according to the tRNA regions that they derive from, namely 3′tRF, 5′tRF, and tRF-halves. Additionally, another tRF subgroup deriving from tRNA precursors has been reported, the 3′U tRFs. tRF length ranges from 17 to 26 nt for the 3′and 5′tRFs, and from 30 to 40 nt for tRF-halves. tRF biogenesis is still not yet elucidated, although there is strong evidence that Dicer (and DICER-LIKE) proteins, as well as other RNases such as Angiogenin in mammal and RNS proteins family in plants, are responsible for processing specific tRFs. In plants, the abundance of those molecules varies among tissues, developmental stages, and environmental conditions. More recently, several studies have contributed to elucidate the role that these intriguing molecules may play in all organisms. Among the recent discoveries, tRFs were found to be involved in distinctive regulatory layers, such as transcription and translation regulation, RNA degradation, ribosome biogenesis, stress response, regulatory signaling in plant nodulation, and genome protection against transposable elements. Although tRF biology is still poorly understood, the field has blossomed in the past few years, and this review summarizes the most recent developments in the tRF field in plants.

Background: For multicellular organisms, much remains unknown about the dynamics of synonymous codon and amino acid use in highly expressed genes, including whether their use varies with expression in different tissue types and sexes. Moreover, specific codons and amino acids may have translational functions in highly transcribed genes, that largely depend on their relationships to tRNA gene copies in the genome. However, these relationships and putative functions are poorly understood, particularly in multicellular systems. Results: Here, we studied codon and amino acid use in highly expressed genes from reproductive and nervous system tissues (male and female gonad, somatic reproductive system, brain and ventral nerve cord, and male accessory glands) in the cricket Gryllus bimaculatus. We report an optimal codon, defined as the codon preferentially used in highly expressed genes, for each of the 18 amino acids with synonymous codons in this organism. The optimal codons were mostly shared among tissue types and both sexes. However, the frequency of optimal codons was highest in gonadal genes. Concordant with translational selection, a majority of the optimal codons had abundant matching tRNA gene copies in the genome, but sometimes obligately required wobble tRNAs. We suggest the latter may comprise a mechanism for slowing translation of abundant transcripts, particularly for cell-cycle genes. Non-optimal codons, defined as those least commonly used in highly transcribed genes, intriguingly often had abundant tRNAs, and had elevated use in a subset of genes with specialized functions (gametic and apoptosis genes), suggesting their use promotes the translational upregulation of particular mRNAs. In terms of amino acids, we found evidence suggesting that amino acid frequency, tRNA gene copy number, and amino acid biosynthetic costs (size/complexity) had all interdependently evolved in this insect model, potentially for translational optimization. Conclusions: Collectively, the results suggest a model whereby codon use in highly expressed genes, including optimal, wobble, and non-optimal codons, and their tRNA abundances, as well as amino acid use, have been influenced by adaptation for various functional roles in translation within this cricket. The effects of expression in different tissue types and the two sexes are discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fifty-six microRNAs (miRNAs) from 33 conserved families and four Fasciola -specific miRNAs were identified. • miRNAs are mainly involved in the regulation of metabolism, biosynthesis, growth and developmental processes. • The expression profiles of 5′ halves derived by tRNA-Lys and tRNA-Gly were mainly related to the buffalo-infecting stages. • This study provided an overview of the dynamic changes of small RNAs that occur during the lifecycle stages of F. gigantica. • This global analysis of F. gigantica lifecycle stages revealed new roles of miRNAs and tRFs in parasite development. The tropical liver fluke Fasciola gigantica affects livestock and humans in many Asian countries, large parts of Africa, and parts of Europe. Despite the public health and economic impacts of F. gigantica , understanding of F. gigantica biology and how the complex lifecycle of this liver fluke is transcriptionally regulated remain unknown. Here, we tested the hypothesis that the regulatory small non-coding RNAs (sncRNAs), microRNAs (miRNAs) and tRNA-derived fragments (tRFs) play roles in the adaptation of F. gigantica to its intermediate and definitive hosts. We sequenced sncRNAs of eight lifecycle stages of F. gigantica. In total, 56 miRNAs from 33 conserved families and four Fasciola -specific miRNAs were identified. Expression analysis of miRNAs suggested clear stage-related patterns. By leveraging the existing transcriptomic data, we predicted a miRNA-based regulation of metabolism, transport, growth and developmental processes. Also, by comparing miRNA complement of F. gigantica with that of Fasciola hepatica , we detected a high level of conservation and identified differences in some miRNAs, which can be used to distinguish the two species. Moreover, we found that tRFs at each lifecycle stage were predominantly derived by tRNA-Lys and tRNA-Gly at 5′ half sites, but relatively high expression was related to the buffalo-infecting stages. Taken together, we provided a comprehensive overview of the dynamic transcriptional changes of small RNAs that occur during the developmental stages of F. gigantica. This global analysis of F. gigantica lifecycle stages revealed new roles of miRNAs and tRFs in parasite development and will facilitate future research into understanding of fasciolosis pathobiology. [ABSTRACT FROM AUTHOR]

Transfer RNA-derived fragments (tRFs) exist in all branches of life. They are involved in RNA degradation, regulation of gene expression, ribosome biogenesis. In archaebacteria, kinetoplastid, yeast, and human cells, they were also shown to regulate translation. In Arabidopsis, the tRFs population fluctuates under developmental or environmental conditions but their functions are yet poorly understood. Here, we show that populations of long (30–35 nt) or short (19–25 nt) tRFs produced from Arabidopsis tRNAs can inhibit in vitro translation of a reporter gene. Analysing a series of oligoribonucleotides mimicking natural tRFs, we demonstrate that only a limited set of tRFs possess the ability to affect protein synthesis. Out of a dozen of tRFs, only two deriving from tRNAAla(AGC) and tRNAAsn(GUU) strongly attenuate translation in vitro. Contrary to human tRF(Ala), the 4 Gs present at the 5ʹ extremity of Arabidopsis tRF(Ala) are not implicated in this inhibition while the G18 and G19 residues are essential. Protein synthesis inhibition by tRFs does not require complementarity with the translated mRNA but, having the capability to be associated with polyribosomes, tRFs likely act as general modulation factors of the translation process in plants. [ABSTRACT FROM AUTHOR]

• A 2D-LC method was firstly developed for purification of individual tRNAs from non-pathogenic E. coli. • Two pure tRNAs were obtained from E. coli MRE600. • Purified tRNAs were characterized as tRNA-Val(UAC) and tRNA-Leu(CAG). • Purified tRNAs showed potent cytotoxic activities toward colorectal cancer cells. Transfer RNAs (tRNAs) are the most abundant class in small non-coding RNAs which have been proved to be pharmacologically active. In the present study, we evaluated the potential anticancer activities of tRNAs from Escherichia coli MRE 600 to investigate the relationship between non-pathogenic Escherichia coli strain and colorectal cancer. To purify individual tRNAs, we firstly developed a two-dimensional liquid chromatography (2D-LC) and successfully obtained two pure tRNAs. Nuclease mediated base-specific digestions coupled with UHPLC–MS/MS techniques led to an identification of these two tRNAs as tRNA-Val(UAC) and tRNA-Leu(CAG) with typical cloverleaf-like secondary structure. MTT assay demonstrated that both tRNA-1 and tRNA-2 exhibit strong cytotoxicity with IC 50 of 113.0 nM and 124.8 nM on HCT-8 cells in a dose-dependent manner. Further clonogenic assay revealed that the purified tRNAs exhibit significant inhibition in colony formation with survival percentage of 79.0 ± 1.6 and 71.2 ± 2.2 at the concentration of 100 nM. These findings provided evidences of anticancer activities of tRNAs from non-pathogenic Escherichia coli strain, indicating that the pharmacological effects of these neglected biomacromolecules from microorganisms should be emphasized. This study put new insights into the therapeutic effects of intestinal microorganism on human diseases, therefore broadened our knowledge of the biological functions of gut microbiota. [ABSTRACT FROM AUTHOR]

Deregulation of tRNAs, aminoacyl-tRNA synthetases (aaRS) or tRNA modifying enzymes, increase the level of protein synthesis errors (PSE) and are associated with several diseases, but the cause-effect mechanisms of these pathologies remain elusive. To clarify the role of PSE in human biology, we have engineered a HEK293 cell line to overexpress a wild type (Wt) tRNASer and two tRNASer mutants that misincorporate serine at non-cognate codon sites. Then, we followed long-term adaptation to PSE of such recombinant cells by analysing cell viability, protein synthesis rate and activation of protein quality control mechanisms (PQC). Engineered cells showed higher level of misfolded and aggregated proteins; activated the ubiquitin-proteasome system (UPS) and the unfolded protein response (UPR), indicative of proteotoxic stress. Adaptation to PSE involved increased protein turnover, UPR up-regulation and altered protein synthesis rate. Gene expression analysis showed that engineered cells presented recurrent alterations in the endoplasmic reticulum, cell adhesion and calcium homeostasis. Herein, we unveil new phenotypic consequences of protein synthesis errors in human cells and identify the protein quality control processes that are necessary for long-term adaptation to PSE and proteotoxic stress. Our data provide important insight on how chronic proteotoxic stress may cause disease and highlight potential biological pathways that support the association of PSE with disease. [ABSTRACT FROM AUTHOR]

The widespread implementation of mass sequencing has revealed a diverse landscape of small RNAs derived from larger precursors. Whilst many of these are likely to be byproducts of degradation, there are nevertheless metabolically stable fragments derived from tRNAs, rRNAs, snoRNAs, and other non-coding RNA, with a number of examples of the production of such fragments being conserved across species. Coupled with specific interactions to RNA-binding proteins and a growing number of experimentally reported examples suggesting function, a case is emerging whereby the biological significance of small non-coding RNAs extends far beyond miRNAs and piRNAs. Related to this, a similarly complex picture is emerging of non-canonical roles for the non-coding precursors, such as for snoRNAs that are also implicated in such areas as the silencing of gene expression and the regulation of alternative splicing. This is in addition to a body of literature describing snoRNAs as an additional source of miRNA-like regulators. This review seeks to highlight emerging roles for such non-coding RNA, focusing specifically on “new” roles for snoRNAs and the small fragments derived from them.

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder that becomes apparent during early childhood development. The complexity of ASD makes clinically diagnosing the condition difficult. Consequently, by identifying the biomarkers associated with ASD severity and combining them with clinical diagnosis, one may better factionalize within the spectrum and devise more targeted therapeutic strategies. Currently, there are no reliable biomarkers that can be used for precise ASD diagnosis. Consequently, our pilot experimental cohort was subdivided into three groups: healthy controls, individuals those that express severe symptoms of ASD, and individuals that exhibit mild symptoms of ASD. Using next-generation sequencing, we were able to identify several circulating non-coding RNAs (cir-ncRNAs) in plasma. To the best of our knowledge, this study is the first to show that miRNAs, piRNAs, snoRNAs, Y-RNAs, tRNAs, and lncRNAs are stably expressed in plasma. Our data identify cir-ncRNAs that are specific to ASD. Furthermore, several of the identified cir-ncRNAs were explicitly associated with either the severe or mild groups. Hence, our findings suggest that cir-ncRNAs have the potential to be utilized as objective diagnostic biomarkers and clinical targets.

Cancer is a leading cause of morbidity and mortality worldwide. While numerous factors have been identified as contributing to the development of malignancy, our understanding of the mechanisms involved remains limited. Early cancer detection and the development of effective treatments are therefore critical areas of research. One class of molecules that play a crucial role in the transmission of genetic information are transfer RNAs (tRNAs), which are the most abundant RNA molecules in the human transcriptome. Dysregulated synthesis of tRNAs directly results in translation disorders and diseases, including cancer. Moreover, various types of tRNA modifications and the enzymes responsible for these modifications have been implicated in tumor biology. Furthermore, alterations in tRNA modification can impact tRNA stability, and impaired stability can prompt the cleavage of tRNAs into smaller fragments known as tRNA fragments (tRFs). Initially believed to be random byproducts lacking any physiological function, tRFs have now been redefined as non-coding RNA molecules with distinct roles in regulating RNA stability, translation, target gene expression, and other biological processes. In this review, we present recent findings on translational regulatory models centered around tRNAs in tumors, providing a deeper understanding of tumorigenesis and suggesting new directions for cancer treatment., Competing Interests: The authors declare no conflicts of interest.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification and tsRNA formation. More specifically, m5U54 hypomodification is followed by overexpression of the ribonuclease angiogenin (ANG) that cleaves tRNAs near the anticodon, resulting in accumulation of 5′tRNA-derived stress-induced RNAs (5′tiRNAs), namely 5′tiRNA-GlyGCC and 5′tiRNA-GluCTC, among others. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tiRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tiRNA formation in mammalian cells. These results establish a link between tRNA hypomethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

The expression of transfer RNAs (tRNAs) is deregulated in cancer cells but the mechanisms and functional meaning of such deregulation are poorly understood. The proteome of cancer cells is not fully encoded by their transcriptome, however, the contribution of mRNA translation to such diversity remains to be elucidated. We review data supporting the hypothesis that tRNA expression deregulation and translational error rate is an important contributor to proteome diversity and cell population heterogeneity, genome instability, and drug resistance in tumors. This hypothesis is aligned with recent data in various model organisms, showing unanticipated adaptive roles of translational errors (adaptive mistranslation), expression control of specific gene subsets by tRNAs, and proteome diversification by elevation of translational error rates in tumors. tRNAs are positively regulated by oncogenes, often being increased in several types of cancer in a tissue-dependent manner, although individual regulation still lacks understanding. Upregulation of specific tRNAs stabilizes transcripts that can be responsible for inducing cancer hallmarks, such as metastasis. tRNA sets are valuable yet still unexplored biomarkers, which can be used to discriminate tumors from normal tissue and to predict patient outcome. tRNA deregulation induces protein synthesis errors, which have been correlated to accelerated tumor growth kinetics. Increased protein errors produced by tRNA imbalance induce cellular reprogramming to mitigate stress, becoming a source of population heterogeneity. [ABSTRACT FROM AUTHOR]

Even before Rosalin Franklin had discovered the DNA double helix, in her impressive X-ray diffraction image pattern, Erwin Schröedinger, described, in his excellent book, What is Life, how the finding of aperiodic crystals in biological systems surprised him (an aperiodic crystal, which, in my opinion is the material carrier of life). In the 21st century and still far from being able to define life, we are attending to a quick acceleration of knowledge on regulatory information. With the discovery of new codes and punctuation marks, we will greatly increase our understanding in front of an impressive avalanche of genomic sequences. Trifonov et al. defined a genetic code as a widespread DNA sequence pattern that carries a message with an impact on biology. These patterns are largely captured in transcribed messages that give meaning and identity to the particular cells. In this review, I will go through my personal career in and after my years of work in the laboratory of Gordon H. Dixon, extending toward the impressive acquisition of new knowledge on regulatory information and genetic codes provided by remarkable scientists in the field. Abbreviations: CA II: carbonic anhydridase II (chicken); Car2: carbonic anhydridase 2 (mouse); CpG islands: short (>0.5 kb) stretches of DNA with a G+C content ≥55%; DNMT1: DNA methyltransferases 1; DNMT3b: DNA methyltransferases 3B; DSB: double-strand DNA breaks; ERT: endogenous retrotransposon; ERV: endogenous retroviruses; ES cells: embryonic stem cells; GAPDH: glyceraldehide phosphate dehydrogenase; H1: histone H1; HATs: histone acetyltransferases; HDACs: histone deacetylases; H3K4me3: histone 3 trimethylated at lys 4; H3K79me2: histone 3 dimethylated at lys 79; HMG: high mobility group proteins; HMT: histone methyltransferase; HP1: heterochromatin protein 1; HR: homologous recombination; HSE: heat-shock element; ICRs: imprinted control regions; IRF: interferon regulatory factor; LDH-A/-B: lactate dehydrogenase A/B; LTR: long terminal repeats; MeCP2: methyl CpG binding protein 2; OCT4: octamer-binding transcription factor 4; PAF1: RNA Polymerase II associated factor 1; piRNA: PIWI-interacting RNA; poly(A) tails: poly-adenine tails; PRC2: polycomb repressive complex 2; PTMs: post-translational modifications; SIRT 1: sirtuin 1, silent information regulator; STAT3: signal transducer and activator of transcription; tRNAs: transfer RNA; tRFs: tRNA-derived fragments; TSS: transcription start site; TE: transposable elements; UB I: polyubiquitin I; UB II: polyubiquitin II; UBE 2N: ubiquitin conjugating enzyme E2N; 5ʹ-UTR: 5ʹ-untranslated sequences; 3ʹ-UTR: 3ʹ-untranslated sequences. [ABSTRACT FROM AUTHOR]

Viruses rely on their host’s translation machinery for the synthesis of their own proteins. Problems belie viral translation when the host has a codon usage bias (CUB) that is different from an infecting virus due to differences in the GC content between the host and virus genomes. Here, we examine the hypothesis that chloroviruses adapted to host CUB by acquisition and selection of tRNAs that at least partially favor their own CUB. The genomes of 41 chloroviruses comprising three clades, each infecting a different algal host, have been sequenced, assembled and annotated. All 41 viruses not only encode tRNAs, but their tRNA genes are located in clusters. While differences were observed between clades and even within clades, seven tRNA genes were common to all three clades of chloroviruses, including the tRNAArg gene, which was found in all 41 chloroviruses. By comparing the codon usage of one chlorovirus algal host, in which the genome has been sequenced and annotated (67% GC content), to that of two of its viruses (40% GC content), we found that the viruses were able to at least partially overcome the host’s CUB by encoding tRNAs that recognize AU-rich codons. Evidence presented herein supports the hypothesis that a chlorovirus tRNA cluster was present in the most recent common ancestor (MRCA) prior to divergence into three clades. In addition, the MRCA encoded a putative isoleucine lysidine synthase (TilS) that remains in 39/41 chloroviruses examined herein, suggesting a strong evolutionary pressure to retain the gene. TilS alters the anticodon of tRNAMet that normally recognizes AUG to then recognize AUA, a codon for isoleucine. This is advantageous to the chloroviruses because the AUA codon is 12–13 times more common in the chloroviruses than their host, further helping the chloroviruses to overcome CUB. Among large DNA viruses infecting eukaryotes, the presence of tRNA genes and tRNA clusters appear to be most common in the Phycodnaviridae and, to a lesser extent, in the Mimiviridae.

Deregulation of tRNAs, aminoacyl-tRNA synthetases and tRNA modifying enzymes are common in cancer, raising the hypothesis that protein synthesis efficiency and accuracy (mistranslation) are compromised in tumors. We show here that human colon tumors and xenograft tumors produced in mice by two epithelial cancer cell lines mistranslate 2- to 4-fold more frequently than normal tissue. To clarify if protein mistranslation plays a role in tumor biology, we expressed mutant Ser-tRNAs that misincorporate Ser-at-Ala (frequent error) and Ser-at-Leu (infrequent error) in NIH3T3 cells and investigated how they responded to the proteome instability generated by the amino acid misincorporations. There was high tolerance to both misreading tRNAs, but the Ser-to-Ala misreading tRNA was a more potent inducer of cell transformation, stimulated angiogenesis and produced faster growing tumors in mice than the Ser-to-Leu misincorporating tRNA. Upregulation of the Akt pathway and the UPR were also observed. Most surprisingly, the relative expression of both misreading tRNAs increased during tumor growth, suggesting that protein mistranslation is advantageous in cancer contexts. These data highlight new features of protein synthesis deregulation in tumor biology. [ABSTRACT FROM AUTHOR]

Previously believed to be mere random degradation products, tRNA-derived small RNAs have been lately connected to a series of functions that include, surprisingly, genome protection against retrotransposons. tRNAs have been known for a long time to be involved in the replication cycle of retroviruses, pararetroviruses and retrotransposons as primers of their reverse transcription. tRNA-derived small RNAs, as functional small RNAs or as mere tRNA degradation products, have emerged as important players in the regulation of genic transcription. Nevertheless, the involvement of functional sRNAs derived from tRNA transcripts in transposon posttranscriptional control is a regulatory layer that remained elusive until now. Here I review the recent discoveries in the field that connect tRNA-derived small RNAs and retrotransposon control. [ABSTRACT FROM PUBLISHER]

Several families of multicopy genes, such as transfer ribonucleic acids (tRNAs) and ribosomal RNAs (rRNAs), are subject to concerted evolution, an effect that keeps sequences of paralogous genes effectively identical. Under these circumstances, it is impossible to distinguish orthologs from paralogs on the basis of sequence similarity alone. Synteny, the preservation of relative genomic locations, however, also remains informative for the disambiguation of evolutionary relationships in this situation. In this contribution, we describe an automatic pipeline for the evolutionary analysis of such cases that use genome-wide alignments as a starting point to assign orthology relationships determined by synteny. The evolution of tRNAs in primates as well as the history of the Y RNA family in vertebrates and nematodes are used to showcase the method. The pipeline is freely available. [ABSTRACT FROM AUTHOR]

RNA-dependent RNA polymerases (RdRp) are very ancient enzymes and are essential for all viruses with RNA genomes. We reconstruct the origin and evolution of this polymerase since the initial stages of the origin of life. The origin of the RdRp was traced back from tRNA ancestors. At the origin of the RdRp the most ancient part of the protein is the cofactor-binding site that had the capacity of binding to simple molecules as magnesium, calcium, and ribonucleotides. Our results suggest that RdRp originated from junctions of proto-tRNAs that worked as the first genes at the emergence of the primitive translation system, where the RNA was the informational molecule. The initial domain, worked as a building block for the emergence of the fingers and thumb domains. From the ancestral RdRp, we could establish the evolutionary stages of viral evolution from a rooted ancestor to modern viruses. It was observed that the selective pressure under the RdRp was the organization and functioning of the genome, where RNA double-stranded and RNA single-stranded virus formed a separate group. We propose an evolutionary route to the polymerases and the results suggest an ancient scenario for the origin of RNA viruses.

Among several smallRNAs classes, microRNAs play an important role in controlling the post-transcriptional events. Next generation sequencing has played a major role in extending the landscape of miRNAs and revealing their spatio-temporal roles in development and abiotic stress. Lateral evolution of these smallRNAs classes have widely been seen with the recently emerging knowledge on tRNA derived smallRNAs. In the present perspective, we discussed classification, identification and roles of tRNA derived smallRNAs across plants and their potential involvement in abiotic and biotic stresses.

RNA-dependent RNA polymerases (RdRp) are very ancient enzymes and are essential for all viruses with RNA genomes. We reconstruct the origin and evolution of this polymerase since the initial stages of the origin of life. The origin of the RdRp was traced back from tRNA ancestors. At the origin of the RdRp the most ancient part of the protein is the cofactor-binding site that had the capacity of binding to simple molecules as magnesium, calcium, and ribonucleotides. Our results suggest that RdRp originated from junctions of proto-tRNAs that worked as the first genes at the emergence of the primitive translation system, where the RNA was the informational molecule. The initial domain, worked as a building block for the emergence of the fingers and thumb domains. From the ancestral RdRp, we could establish the evolutionary stages of viral evolution from a rooted ancestor to modern viruses. It was observed that the selective pressure under the RdRp was the organization and functioning of the genome, where RNA double-stranded and RNA single-stranded virus formed a separate group. We propose an evolutionary route to the polymerases and the results suggest an ancient scenario for the origin of RNA viruses. [ABSTRACT FROM AUTHOR]

The functional relationship between tRNAs and retrotransposons have been known for more than 35 years. tRNAs are used as primer molecules to guide the reverse transcription of retrotransposons. Recently, tRNAs have also emerge as important players in the postranscriptional regulation of retrotransposons by means of tRNA-derived small RNAs. This surprisingly new layer of regulation indicates that tRNAs are used both in the promotion and the suppression of the reverse transcription of retrotransposons indicating their primary role in the life cycle of LTR retrotransposons. This adds another level of translational control to tRNAs. Here we review the different known levels of interactions of tRNAs and retrotransposons and highlight the unknown parts of this interaction. [ABSTRACT FROM PUBLISHER]

Among several smallRNAs classes, microRNAs play an important role in controlling the post-transcriptional events. Next generation sequencing has played a major role in extending the landscape of miRNAs and revealing their spatio-temporal roles in development and abiotic stress. Lateral evolution of these smallRNAs classes have widely been seen with the recently emerging knowledge on tRNA derived smallRNAs. In the present perspective, we discussed classification, identification and roles of tRNA derived smallRNAs across plants and their potential involvement in abiotic and biotic stresses. [ABSTRACT FROM AUTHOR]

Amygdalus mira (Koehne) Ricker (Basionym: Prunus mira Koehne) is a wild relative species of peach belonging to Rosaceae family. It is likely the oldest progenitor of peach and considered threatened or even on the verge of extinction, which requires urgent conservation attention. To contribute to such efforts, complete chloroplast genome of A. mira was assembled using Illumina Hiseq 2500 platform. The cpDNA genome is 157,330 bp in length and has a GC content of 36.80%, with a typical circular quadripartite structure comprising a pair of inverted repeats (IRA and IRB) separated by two single-copy regions. The cpDNA genome consisted of 88 coding sequences (CDS), 37 tRNAs and 8 rRNAs genes. 583 simple sequence repeat (SSR) motifs were identified, where hexa-nucleotide was the most common (27.7% of all SSRs). The complete cpDNA genome of A. mira will be of valuable data for the upcoming research on comparative population genomics of peach. [ABSTRACT FROM AUTHOR]