Transcriptome-wide analysis of roles for tRNA modifications in translational regulation

Covalent nucleotide modifications in noncoding RNAs such as tRNAs affect a plethora of biological processes, with new functions continuing to be discovered for even well-known tRNA modifications. To systematically compare the functions of a large set of ncRNA modifications in gene regulation, we carried out ribosome profiling and RNA-Seq in budding yeast for 57 nonessential genes involved in tRNA modification. Deletion mutants exhibited a range of translational phenotypes, with modifying 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 novel roles for tRNA modifying enzymes in transcriptional 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.