Trm9-catalyzed tRNA modifications link translation to the DNA damage response.
Transcriptional and posttranslational signals are known mechanisms that promote efficient responses to DNA damage. We have identified Saccharomyces cerevisiae tRNA methyltransferase 9 (Trm9) as an enzyme that prevents cell death via translational enhancement of DNA damage response proteins. Trm9 methylates the uridine wobble base of tRNAARG(UCU) and tRNAGLU(UUC). We used computational and molecular approaches to predict that Trm9 enhances the translation of some transcripts overrepresented with specific arginine and glutamic acid codons. We found that translation elongation factor 3 (YEF3) and the ribonucleotide reductase (RNR1 and RNR3) large subunits are overrepresented with specific arginine and glutamic acid codons, and we demonstrated that Trm9 significantly enhances Yef3, Rnr1, and Rnr3 protein levels. Additionally, we identified 425 genes, which included YEF3, RNR1, and RNR3, with a unique codon usage pattern linked to Trm9. We propose that Trm9-specific tRNA modifications enhance codon-specific translation elongation and promote increased levels of key damage response proteins.
Begley
Ulrike
U
Department of Biomedical Sciences, GenNYsis Center for Excellence in Cancer Genomics, University at Albany, State University of New York, Rensselaer, NY 12144, USA.
Dyavaiah
Madhu
M
Patil
Ashish
A
Rooney
John P
JP
DiRenzo
Dan
D
Young
Christine M
CM
Conklin
Douglas S
DS
Zitomer
Richard S
RS
Begley
Thomas J
TJ
D002384:Catalysis; D003062:Codon; D004249:DNA Damage; D008745:Methylation; D010441:Peptide Chain Elongation, Translational; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012347:RNA, Transfer, Arg / Q000378:metabolism*; D012352:RNA, Transfer, Glu / Q000378:metabolism*; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism*
D003062:Codon; D010445:Peptide Elongation Factors; D012347:RNA, Transfer, Arg; D012352:RNA, Transfer, Glu; D029701:Saccharomyces cerevisiae Proteins; C111584:YEF3 protein, S cerevisiae; C517042:RNR3 protein, S cerevisiae; D012262:Ribonucleoside Diphosphate Reductase; C480488:TRM9 protein, S cerevisiae; D012359:tRNA Methyltransferases; D001616:beta-Galactosidase