title: tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding.
abstract: tRNA modifications are crucial to ensure translation efficiency and fidelity. In eukaryotes, the URM1 and ELP pathways increase cellular resistance to various stress conditions, such as nutrient starvation and oxidative agents, by promoting thiolation and methoxycarbonylmethylation, respectively, of the wobble uridine of cytoplasmic (tK(UUU)), (tQ(UUG)), and (tE(UUC)). Although in vitro experiments have implicated these tRNA modifications in modulating wobbling capacity and translation efficiency, their exact in vivo biological roles remain largely unexplored. Using a combination of quantitative proteomics and codon-specific translation reporters, we find that translation of a specific gene subset enriched for AAA, CAA, and GAA codons is impaired in the absence of URM1- and ELP-dependent tRNA modifications. Moreover, in vitro experiments using native tRNAs demonstrate that both modifications enhance binding of tK(UUU) to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.
authors.affiliation: Department of Biology, Institute of Biochemistry, Eidgenössiche Technische Hochschule Zürich, 8093 Zürich, Switzerland.
authors.forename: Vanessa Anissa Nathalie
authors.initials: VA
authors.lastname: Rezgui
authors.forename: Kshitiz
authors.initials: K
authors.lastname: Tyagi
authors.forename: Namit
authors.initials: N
authors.lastname: Ranjan
authors.forename: Andrey L
authors.initials: AL
authors.lastname: Konevega
authors.forename: Joerg
authors.initials: J
authors.lastname: Mittelstaet
authors.forename: Marina V
authors.initials: MV
authors.lastname: Rodnina
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
authors.forename: Patrick G A
authors.initials: PG
authors.lastname: Pedrioli
mesh_terms: D001665:Binding Sites; D003062:Codon; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D003062:Codon; D011506:Proteins; D012333:RNA, Messenger; D012343:RNA, Transfer
keywords: SILAC; systems biology; translation regulation