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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    • "[21– 23]). During their nuclear biogenesis, pre-tRNAs undergo various maturation steps including cleavage of the 5′ leader sequence by RNase P, RNase Z-dependent 3′ end processing, 3′ CCA addition and introduction of a myriad of nucleotide modifications (reviewed in Ref. [24]). Interestingly, in yeast, splicing of intron-containing tRNAs takes place on the mitochondrial outer surface [25] [26], whereas in mammalian cells, the tRNA splicing machinery is located within the nucleus [27] and intron removal takes place prior to export through the NPC. "
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    ABSTRACT: RNAs and ribonucleoprotein complexes (RNPs) play key roles in mediating and regulating gene expression. In eukaryotes, most RNAs are transcribed, processed and assembled with proteins in the nucleus and then either function in the cytoplasm or also undergo a cytoplasmic phase in their biogenesis. This compartmentalisation ensures that sequential steps in gene expression and RNP production are performed in the correct order and allows important quality control mechanisms that prevent the involvement of aberrant RNAs/RNPs in these cellular pathways. The selective exchange of RNAs/RNPs between the nucleus and cytoplasm is enabled by nuclear pore complexes (NPCs), which function as gateways between these compartments. RNA/RNP transport is facilitated by a range of nuclear transport receptors and adaptors, which are specifically recruited to their cargos and mediate interactions with nucleoporins to allow directional translocation through NPCs. While some transport factors are only responsible for the export/import of a certain class of RNA/RNP, others are multifunctional and, in the case of large RNPs, several export factors appear to work together to bring about export. Recent structural studies have revealed aspects of the mechanisms employed by transport receptors to enable specific cargo recognition, and genome-wide approaches have provided the first insights into the diverse composition of pre-mRNPs during export. Furthermore, the regulation of RNA/RNP export is emerging as an important means to modulate gene expression in stress conditions and disease.
    Journal of Molecular Biology 10/2015; DOI:10.1016/j.jmb.2015.09.023 · 4.33 Impact Factor
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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
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