Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation
Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine; Garber Lab
Amino Acids, Peptides, and Proteins | Bioinformatics | Computational Biology | Enzymes and Coenzymes | Genetic Phenomena | Genomics | Integrative Biology | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides
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.
RNA modifications, noncoding RNA, protein translation, ribosome profiling, tRNA
DOI of Published Version
Mol Cell. 2017 Dec 7;68(5):978-992.e4. doi: 10.1016/j.molcel.2017.11.002. Epub 2017 Nov 30. Link to article on publisher's site
Chou, Hsin-Jung; Donnard, Elisa; Gustafsson, H. Tobias; Garber, Manuel; and Rando, Oliver J., "Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation" (2017). Garber Lab Publications. 7.