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PMID: 29198561 Published · ppublish English Journal Article

Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation.

Molecular cell ·Vol. 68 ·No. 5 ·2017-12-07 ·Pages 978-992.e4

Chou HJ, Donnard E, Gustafsson HT, Garber M, Rando OJ

Abstract

Covalent nucleotide modifications in noncoding RNAs affect a plethora of biological processes, and new functions continue to be discovered even for well-known modifying enzymes. To systematically compare the functions of a large set of noncoding RNA modifications in gene regulation, we carried out ribosome profiling in budding yeast to characterize 57 nonessential genes involved in tRNA modification. Deletion mutants exhibited a range of translational phenotypes, with enzymes known to modify anticodons, or non-tRNA substrates such as rRNA, exhibiting the most dramatic translational perturbations. Our data build on prior reports documenting translational upregulation of the nutrient-responsive transcription factor Gcn4 in response to numerous tRNA perturbations, and identify many additional translationally regulated mRNAs throughout the yeast genome. Our data also uncover unexpected roles for tRNA-modifying enzymes in regulation of TY retroelements, and in rRNA 2'-O-methylation. This dataset should provide a rich resource for discovery of additional links between tRNA modifications and gene regulation.

Keywords
RNA modifications noncoding RNA protein translation ribosome profiling tRNA
MeSH Terms
Basic-Leucine Zipper Transcription Factors/biosynthesis,genetics Gene Expression Profiling/methods Gene Expression Regulation, Fungal Genotype Methylation Mutation Phenotype RNA, Fungal/genetics,metabolism RNA, Messenger/genetics,metabolism RNA, Ribosomal/genetics,metabolism RNA, Transfer/genetics,metabolism RNA, Untranslated/genetics,metabolism Retroelements Ribosomes/enzymology,genetics Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins/biosynthesis,genetics,metabolism Terminal Repeat Sequences Transcriptome tRNA Methyltransferases/genetics,metabolism
Chemicals
Basic-Leucine Zipper Transcription Factors GCN4 protein, S cerevisiae RNA, Fungal RNA, Messenger RNA, Ribosomal RNA, Untranslated Retroelements Saccharomyces cerevisiae Proteins RNA, Transfer Trm7 protein, S cerevisiae tRNA Methyltransferases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chou Hsin-Jung
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Donnard Elisa
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Gustafsson H Tobias
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Garber Manuel
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Rando Oliver J
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: oliver.rando@umassmed.edu.
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2017.11.002
Email
oliver.rando@umassmed.edu
Published
2017-12-07
Epub
2017-00-30
Pages
978-992.e4
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC5728682
Subset
IM
Grants
NIEHS NIH HHS · DP1 ES025458 · United States
NIGMS NIH HHS · R01 GM079205 · United States
NICHD NIH HHS · R01 HD080224 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2017.11.002 PMC Full Text View journal details
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