Editing of misaminoacylated tRNA controls the sensitivity of amino acid stress responses in Saccharomyces cerevisiae. Issue 7 (7th February 2017)

• Record Type: Journal Article
• Authors: Mohler, Kyle; Mann, Rebecca; Bullwinkle, Tammy J.; Hopkins, Kyle; Hwang, Lin; Reynolds, Noah M.; Gassaway, Brandon; Aerni, Hans-Rudolf; Rinehart, Jesse; Polymenis, Michael; Faull, Kym; Ibba, Michael
• Is Part Of: Nucleic acids research. Volume 45:Issue 7(2017)
• Page Start: 3985
• Page End: 3996
• Publication Date: 2017-02-07
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx077
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Amino acid starvation activates the protein kinase Gcn2p, leading to changes in gene expression and translation. Gcn2p is activated by deacylated tRNA, which accumulates when tRNA aminoacylation is limited by lack of substrates or inhibition of synthesis. Pairing of amino acids and deacylated tRNAs is catalyzed by aminoacyl-tRNA synthetases, which use quality control pathways to maintain substrate specificity. Phenylalanyl-tRNA synthetase (PheRS) maintains specificity via an editing pathway that targets non-cognate Tyr-tRNA Phe . While the primary role of aaRS editing is to prevent misaminoacylation, we demonstrate editing of misaminoacylated tRNA is also required for detection of amino acid starvation by Gcn2p. Ablation of PheRS editing caused accumulation of Tyr-tRNA Phe (5%), but not deacylated tRNA Phe during amino acid starvation, limiting Gcn2p kinase activity and suppressing Gcn4p-dependent gene expression. While the PheRS-editing ablated strain grew 50% slower and displayed a 27-fold increase in the rate of mistranslation of Phe codons as Tyr compared to wild type, the increase in mistranslation was insufficient to activate an unfolded protein stress response. These findings show that during amino acid starvation a primary role of aaRS quality control is to help the cell mount an effective stress response, independent of the role of editing in maintaining translational accuracy.