TY - JOUR
T1 - TRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding
AU - Rezgui, Vanessa Anissa Nathalie
AU - Tyagi, Kshitiz
AU - Ranjan, Namit
AU - Konevega, Audrey L.
AU - Mittelstaet, Joerg
AU - Rodnina, Marina V.
AU - Peter, Matthias
AU - Pedrioli, P.G.A.
PY - 2013/7/23
Y1 - 2013/7/23
N2 - 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 tRNAUUU Lys (tK), tRNAUUG Gln (tQ), and tRNAUUC Glu (tE). 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 to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.
AB - 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 tRNAUUU Lys (tK), tRNAUUG Gln (tQ), and tRNAUUC Glu (tE). 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 to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.
UR - http://www.scopus.com/inward/record.url?scp=84880672169&partnerID=8YFLogxK
U2 - 10.1073/pnas.1300781110
DO - 10.1073/pnas.1300781110
M3 - Article
C2 - 23836657
AN - SCOPUS:84880672169
SN - 0027-8424
VL - 110
SP - 12289
EP - 12294
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 30
ER -