tRNA-Derived RNA Fragments Associate with Human Multisynthetase Complex (MSC) and Modulate Ribosomal Protein Translation.

The functionality of small RNAs from abundant species of "housekeeping" noncoding RNAs (e.g., rRNA, tRNA, snRNA, snoRNA, etc.) remains a highly studied topic. The current state of research on short RNAs derived from transfer RNA (tRNA), called tRNA-derived fragments (tRFs), has been restricted largely to expression studies and limited functional studies. 5' tRFs are known translational inhibitors in mammalian cells, yet little is known about their functionality. Here we report on the first experimental evidence of the tRF protein interactome, identifying the mammalian multisynthetase complex as the primary interactor of the 5' tRF Gln19. We also present proteome-wide SILAC evidence that 5' tRFs increase ribosomal and poly(A)-binding protein translation.

[1]  Rogerio Margis,et al.  Description of plant tRNA-derived RNA fragments (tRFs) associated with argonaute and identification of their putative targets , 2013, Biology Direct.

[2]  Steven P Gygi,et al.  Angiogenin-induced tRNA fragments inhibit translation initiation. , 2011, Molecular cell.

[3]  M. Mirande,et al.  Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the Cytoplasm of Human Cells* , 2009, Journal of Biological Chemistry.

[4]  Israel Steinfeld,et al.  BMC Bioinformatics BioMed Central , 2008 .

[5]  J. Yewdell,et al.  RNA Binding Targets Aminoacyl-tRNA Synthetases to Translating Ribosomes* , 2011, The Journal of Biological Chemistry.

[6]  G. Barton,et al.  Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. , 2009, RNA.

[7]  Gyorgy Hutvagner,et al.  tRNA-Derived Fragments (tRFs): Emerging New Roles for an Ancient RNA in the Regulation of Gene Expression , 2015, Life.

[8]  Paul Schimmel,et al.  Essential nontranslational functions of tRNA synthetases. , 2013, Nature chemical biology.

[9]  M. Mirande.  Processivity of translation in the eukaryote cell: Role of aminoacyl‐tRNA synthetases , 2010, FEBS letters.

[10]  Andrea Califano,et al.  tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma , 2013, Proceedings of the National Academy of Sciences.

[11]  S. Le,et al.  Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: evidence for the processing of a viral-cellular double-stranded RNA hybrid , 2009, Nucleic acids research.

[12]  K. Fujii,et al.  A role for ubiquitin in the clearance of nonfunctional rRNAs. , 2009, Genes & development.

[13]  M. Deutscher,et al.  Channeling of aminoacyl-tRNA for protein synthesis in vivo. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Perona,et al.  tRNA-dependent active site assembly in a class I aminoacyl-tRNA synthetase. , 2003, Structure.

[15]  Lisa Fish,et al.  Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement , 2015, Cell.

[16]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[17]  G. Hutvagner,et al.  Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells , 2013, RNA biology.

[18]  Jürgen Cox,et al.  A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics , 2009, Nature Protocols.

[19]  Zohar Yakhini,et al.  Discovering Motifs in Ranked Lists of DNA Sequences , 2007, PLoS Comput. Biol..

[20]  Thurston H. Y. Dang,et al.  The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells , 2014, Nucleic acids research.

[21]  T. Speed,et al.  A Tetrahymena Piwi bound to mature tRNA 3' fragments activates the exonuclease Xrn2 for RNA processing in the nucleus. , 2012, Molecular cell.

[22]  Sunghoon Kim,et al.  Aminoacyl-tRNA synthetase complexes: beyond translation , 2004, Journal of Cell Science.

[23]  M. Campbell,et al.  PANTHER: a library of protein families and subfamilies indexed by function. , 2003, Genome research.

[24]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[25]  Yan Li,et al.  Both endo-siRNAs and tRNA-derived small RNAs are involved in the differentiation of primitive eukaryote Giardia lamblia , 2014, Proceedings of the National Academy of Sciences.

[26]  R. Sachidanandam,et al.  A growth-essential Tetrahymena Piwi protein carries tRNA fragment cargo. , 2010, Genes & development.

[27]  D. Haussecker,et al.  Human tRNA-derived small RNAs in the global regulation of RNA silencing. , 2010, RNA.

[28]  Sunghoon Kim,et al.  Nucleolar Localization of Human Methionyl–Trna Synthetase and Its Role in Ribosomal RNA Synthesis , 2000, The Journal of cell biology.

[29]  M. Mann,et al.  MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification , 2008, Nature Biotechnology.

[30]  A. Malhotra,et al.  A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). , 2009, Genes & development.

[31]  N. Polacek,et al.  tRNA-Derived Fragments Target the Ribosome and Function as Regulatory Non-Coding RNA in Haloferax volcanii , 2012, Archaea.

[32]  Yuan Chang,et al.  Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs , 2012, Nucleic acids research.