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      Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification

      review-article
      , *
      RNA Biology
      Taylor & Francis
      cerevisiae, modification, Tad2, tRNA, Trm7, Trm8, Trm9, Trm61, Trm112, Trm734

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          Abstract

          tRNA modifications are crucial for efficient and accurate protein translation, with defects often linked to disease. There are 7 cytoplasmic tRNA modifications in the yeast Saccharomyces cerevisiae that are formed by an enzyme consisting of a catalytic subunit and an auxiliary protein, 5 of which require only a single subunit in bacteria, and 2 of which are not found in bacteria. These enzymes include the deaminase Tad2-Tad3, and the methyltransferases Trm6-Trm61, Trm8-Trm82, Trm7-Trm732, and Trm7-Trm734, Trm9-Trm112, and Trm11-Trm112. We describe the occurrence and biological role of each modification, evidence for a required partner protein in S. cerevisiae and other eukaryotes, evidence for a single subunit in bacteria, and evidence for the role of the non-catalytic binding partner. Although it is unclear why these eukaryotic enzymes require partner proteins, studies of some 2-subunit modification enzymes suggest that the partner proteins help expand substrate range or allow integration of cellular activities.

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          Most cited references110

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          GtRNAdb: a database of transfer RNA genes detected in genomic sequence

          Transfer RNAs (tRNAs) represent the single largest, best-understood class of non-protein coding RNA genes found in all living organisms. By far, the major source of new tRNAs is computational identification of genes within newly sequenced genomes. To organize the rapidly growing collection and enable systematic analyses, we created the Genomic tRNA Database (GtRNAdb), currently including over 74 000 tRNA genes predicted from 740 species. The web resource provides overview statistics of tRNA genes within each analyzed genome, including information by isotype and genetic locus, easily downloadable primary sequences, graphical secondary structures and multiple sequence alignments. Direct links for each gene to UCSC eukaryotic and microbial genome browsers provide graphical display of tRNA genes in the context of all other local genetic information. The database can be searched by primary sequence similarity, tRNA characteristics or phylogenetic group. The database is publicly available at http://gtrnadb.ucsc.edu.
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            RNA degradation by the exosome is promoted by a nuclear polyadenylation complex.

            The exosome complex of 3'-5' exonucleases participates in RNA maturation and quality control and can rapidly degrade RNA-protein complexes in vivo. However, the purified exosome showed weak in vitro activity, indicating that rapid RNA degradation requires activating cofactors. This work identifies a nuclear polyadenylation complex containing a known exosome cofactor, the RNA helicase Mtr4p; a poly(A) polymerase, Trf4p; and a zinc knuckle protein, Air2p. In vitro, the Trf4p/Air2p/Mtr4p polyadenylation complex (TRAMP) showed distributive RNA polyadenylation activity. The presence of the exosome suppressed poly(A) tail addition, while TRAMP stimulated exosome degradation through structured RNA substrates. In vivo analyses showed that TRAMP is required for polyadenylation and degradation of rRNA and snoRNA precursors that are characterized exosome substrates. Poly(A) tails stimulate RNA degradation in bacteria, suggesting that this is their ancestral function. We speculate that this function was maintained in eukaryotic nuclei, while cytoplasmic mRNA poly(A) tails acquired different roles in translation.
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              Biosynthesis and function of posttranscriptional modifications of transfer RNAs.

              Posttranscriptional modifications of transfer RNAs (tRNAs) are critical for all core aspects of tRNA function, such as folding, stability, and decoding. Most tRNA modifications were discovered in the 1970s; however, the near-complete description of the genes required to introduce the full set of modifications in both yeast and Escherichia coli is very recent. This led to a new appreciation of the key roles of tRNA modifications and tRNA modification enzymes as checkpoints for tRNA integrity and for integrating translation with other cellular functions such as transcription, primary metabolism, and stress resistance. A global survey of tRNA modification enzymes shows that the functional constraints that drive the presence of modifications are often conserved, but the solutions used to fulfill these constraints differ among different kingdoms, organisms, and species.
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                Author and article information

                Journal
                RNA Biol
                RNA Biol
                KRNB
                RNA Biology
                Taylor & Francis
                1547-6286
                1555-8584
                December 2014
                27 January 2015
                : 11
                : 12 , RNA modifications
                : 1608-1618
                Affiliations
                Department of Biochemistry and Biophysics; Center for RNA Biology; University of Rochester School of Medicine ; Rochester, NY USA
                Author notes
                [* ]Correspondence to: Eric M Phizicky; Email: eric_phizicky@ 123456urmc.rochester.edu
                Article
                1008360
                10.1080/15476286.2015.1008360
                4615748
                25625329
                102c33fb-681d-4ea6-a448-85334511dda9
                © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC© Michael P Guy and Eric M Phizicky

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 14 November 2014
                : 13 December 2014
                : 16 December 2014
                Page count
                Figures: 3, Tables: 1, References: 122, Pages: 11
                Categories
                Review

                Molecular biology
                cerevisiae, modification,tad2,trna,trm7,trm8,trm9,trm61,trm112,trm734
                Molecular biology
                cerevisiae, modification, tad2, trna, trm7, trm8, trm9, trm61, trm112, trm734

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