tRNA biology charges to the front

Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Genes & development (Impact Factor: 10.8). 09/2010; 24(17):1832-60. DOI: 10.1101/gad.1956510
Source: PubMed


tRNA biology has come of age, revealing an unprecedented level of understanding and many unexpected discoveries along the way. This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications. Topics of special focus include the regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions, emerging evidence of signaling pathways involving tRNA and cleavage fragments, and the sophisticated intracellular tRNA trafficking that occurs during and after biosynthesis.

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    • "The extent and order of the different processing steps and their subcellular localization can vary between organisms (Wolin and Matera 1999; Phizicky and Hopper 2010). In addition , certain tRNA genes also carry intronic elements that must be removed in order to generate a functional RNA. "
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    ABSTRACT: We report the discovery of a class of abundant circular noncoding RNAs that are produced during metazoan tRNA splicing. These transcripts, termed tRNA intronic circular (tric)RNAs, are conserved features of animal transcriptomes. Biogenesis of tricRNAs requires anciently conserved tRNA sequence motifs and processing enzymes, and their expression is regulated in an age-dependent and tissue-specific manner. Furthermore, we exploited this biogenesis pathway to develop an in vivo expression system for generating "designer" circular RNAs in human cells. Reporter constructs expressing RNA aptamers such as Spinach and Broccoli can be used to follow the transcription and subcellular localization of tricRNAs in living cells. Owing to the superior stability of circular vs. linear RNA isoforms, this expression system has a wide range of potential applications, from basic research to pharmaceutical science. © 2015 Lu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
    RNA 07/2015; 21(9). DOI:10.1261/rna.052944.115 · 4.94 Impact Factor
    • "molecules between messenger RNAs (mRNAs) and elongating peptide chains on active ribosomes. The biosynthesis and maturation process of tRNAs is a complex and multistep process (for reviews [1] [2] [3] [4] [5]). Although synthesis and maturation of tRNA vary significantly among organelles, organisms, and kingdoms [2], many common features have been retained during evolution . "
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    ABSTRACT: The enzymes of the TrmI family catalyze the formation of the m(1)A58 modification in tRNA. We previously solved the crystal structure of the Thermus thermophilus enzyme and conducted a biophysical study to characterize the interaction between TrmI and tRNA. TrmI enzymes are active as a tetramer and up to two tRNAs can bind to TrmI simultaneously. In this paper, we present the structures of two TrmI mutants (D170A and Y78A). These residues are conserved in the active site of TrmIs and their mutations result in a dramatic alteration of TrmI activity. Both structures of TrmI mutants revealed the flexibility of the N-terminal domain that is probably important to bind tRNA. The structure of TrmI Y78A catalytic domain is unmodified regarding the binding of the SAM co-factor and the conformation of residues potentially interacting with the substrate adenine. This structure reinforces the previously proposed role of Y78, i.e. stabilize the conformation of the A58 ribose needed to hold the adenosine in the active site. The structure of the D170A mutant shows a flexible active site with one loop occupying in part the place of the co-factor and the second loop moving at the entrance to the active site. This structure and recent data confirms the central role of D170 residue binding the amino moiety of SAM and the exocyclic amino group of adenine. Possible mechanisms for methyl transfer are then discussed. Copyright © 2015 Elsevier B.V. All rights reserved.
    Biophysical chemistry 07/2015; DOI:10.1016/j.bpc.2015.06.012 · 1.99 Impact Factor
    • "tRNA genes are transcribed by polymerase III as precursor molecules (pre-tRNA) that undergo end processing and numerous modification steps to mature. Nuclear tRNA processing starts with removal of the 5 ′ -leader sequence by RNase P and trimming of the 3 ′ -trailer sequence (Phizicky and Hopper 2010; Betat et al. 2014). In eukaryotes, 3 ′ end tRNA processing occurs predominantly endonucleolytically and is best studied in Saccharomyces cerevisiae, where these cleavage reactions are carried out by the endonuclease tRNAse Z (Trz1) (Chen et al. 2005; Skowronek et al. 2014), while in humans, the two tRNAse Z homologs, ELAC1 and ELAC2, harbor tRNAse Z activity in vitro (Takaku et al. 2003). "
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    ABSTRACT: Many cellular RNAs require modification of specific residues for their biogenesis, structure, and function. 5-methylcytosine (m(5)C) is a common chemical modification in DNA and RNA but in contrast to the DNA modifying enzymes, only little is known about the methyltransferases that establish m(5)C modifications in RNA. The putative RNA methyltransferase NSUN6 belongs to the family of Nol1/Nop2/SUN domain (NSUN) proteins, but so far its cellular function has remained unknown. To reveal the target spectrum of human NSUN6, we applied UV crosslinking and analysis of cDNA (CRAC) as well as chemical crosslinking with 5-azacytidine. We found that human NSUN6 is associated with tRNAs and acts as a tRNA methyltransferase. Furthermore, we uncovered tRNA(Cys) and tRNA(Thr) as RNA substrates of NSUN6 and identified the cytosine C72 at the 3' end of the tRNA acceptor stem as the target nucleoside. Interestingly, target recognition in vitro depends on the presence of the 3'-CCA tail. Together with the finding that NSUN6 localizes to the cytoplasm and largely colocalizes with marker proteins for the Golgi apparatus and pericentriolar matrix, our data suggest that NSUN6 modifies tRNAs in a late step in their biogenesis. © 2015 Haag et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
    RNA 07/2015; 21(9). DOI:10.1261/rna.051524.115 · 4.94 Impact Factor
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