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      Noncanonical Roles of tRNAs: tRNA Fragments and Beyond

      Author(s): 1 , 1 , 1 , 1
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      Journal: Annual Review of Genetics
      Publisher: Annual Reviews

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          Abstract

          As one of the most abundant and conserved RNA species, transfer RNAs (tRNAs) are well known for their role in reading the codons on messenger RNAs and translating them into proteins. In this review, we discuss the noncanonical functions of tRNAs. These include tRNAs as precursors to novel small RNA molecules derived from tRNAs, also called tRNA-derived fragments, that are abundant across species and have diverse functions in different biological processes, including regulating protein translation, Argonaute-dependent gene silencing, and more. Furthermore, the role of tRNAs in biosynthesis and other regulatory pathways, including nutrient sensing, splicing, transcription, retroelement regulation, immune response, and apoptosis, is reviewed. Genome organization and sequence variation of tRNA genes are also discussed in light of their noncanonical functions. Lastly, we discuss the recent applications of tRNAs in genome editing and microbiome sequencing.

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          Shedding light on the cell biology of extracellular vesicles

          Guillaume van Niel, Gisela D'Angelo, Graça Raposo (2018)
          Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
          Article 0 comments Cited 2558 times – based on 0 reviews     Review now
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            Reassessment of Exosome Composition

            Dennis Jeppesen, Aidan M. Fenix, Jeffrey L. Franklin … (2019)
            The heterogeneity of small extracellular vesicles and presence of non-vesicular extracellular matter have led to debate about contents and functional properties of exosomes. Here, we employ high-resolution density gradient fractionation and direct immunoaffinity capture to precisely characterize the RNA, DNA, and protein constituents of exosomes and other non-vesicle material. Extracellular RNA, RNA-binding proteins and other cellular proteins are differentially expressed in exosomes and non-vesicle compartments. Argonaute 1–4, glycolytic enzymes and cytoskeletal proteins are absent from exosomes. We identify Annexin A1 as a specific marker for microvesicles that are shed directly from the plasma membrane. We further show that small extracellular vesicles are not vehicles of active DNA release. Instead, we propose a new model for active secretion of extracellular DNA through an autophagy- and multivesicular endosome-dependent, but exosome-independent mechanism. This study demonstrates the need for a reassessment of exosome composition and offers a framework for a clearer understanding of extracellular vesicle heterogeneity. A reassessment of exosome composition establishes the differential distribution of protein, RNA, and DNA between small extracellular vesicles and non-vesicular extracellular matter and establishes that small extracellular vesicles are not vehicles of active DNA release.
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              MODOMICS: a database of RNA modification pathways. 2017 update

              Pietro Boccaletto, Magdalena A. Machnicka, Elzbieta Purta … (2017)
              Abstract MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. In the current database version, we included the following new features and data: extended mass spectrometry and liquid chromatography data for modified nucleosides; links between human tRNA sequences and MINTbase - a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments; new, machine-friendly system of unified abbreviations for modified nucleoside names; sets of modified tRNA sequences for two bacterial species, updated collection of mammalian tRNA modifications, 19 newly identified modified ribonucleosides and 66 functionally characterized proteins involved in RNA modification. Data from MODOMICS have been linked to the RNAcentral database of RNA sequences. MODOMICS is available at http://modomics.genesilico.pl.
              Article 0 comments Cited 627 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Title: Annual Review of Genetics
                Abbreviated Title: Annu. Rev. Genet.
                Publisher: Annual Reviews
                ISSN (Print): 0066-4197
                ISSN (Electronic): 1545-2948
                Publication date Created: November 23 2020
                Publication date (Print): November 23 2020
                Volume: 54
                Issue: 1
                Pages: 47-69
                Affiliations
                [1 ]Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia 22901, USA;, , ,
                Article
                DOI: 10.1146/annurev-genet-022620-101840
                PubMed ID: 32841070
                SO-VID: 485e29ae-64ae-4acf-8275-6ae414b976b3
                Copyright © © 2020
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