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

Mol Cell. 2017 Dec 7;68(5):978-992.e4. doi: 10.1016/j.molcel.2017.11.002. Epub 2017 Nov 30.

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
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Fungal
  • Genotype
  • Methylation
  • Mutation
  • Phenotype
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Retroelements
  • Ribosomes / enzymology*
  • Ribosomes / genetics
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / biosynthesis
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Terminal Repeat Sequences
  • Transcriptome*
  • tRNA Methyltransferases / genetics
  • tRNA Methyltransferases / metabolism*

Substances

  • 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