The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications

• Published in: RNA (Cambridge) Vol. 18; no. 10; pp. 1886 - 1896
• Main Authors: Dewe, Joshua M., Whipple, Joseph M., Chernyakov, Irina, Jaramillo, Laura N., Phizicky, Eric M.
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.10.2012
• Subjects: Binding, Competitive - physiology; Metabolic Networks and Pathways - genetics; Metabolic Networks and Pathways - physiology; Mutant Proteins - metabolism; Mutant Proteins - physiology; Organisms, Genetically Modified; Peptide Elongation Factor 1 - genetics; Peptide Elongation Factor 1 - metabolism; Peptide Elongation Factor 1 - physiology; Peptide Elongation Factors - genetics; Peptide Elongation Factors - metabolism; Peptide Elongation Factors - physiology; Protein Binding; RNA Processing, Post-Transcriptional - genetics; RNA Processing, Post-Transcriptional - physiology; RNA Stability - genetics; RNA Stability - physiology; RNA, Transfer - chemistry; RNA, Transfer - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Substrate Specificity; Transfection; tRNA Methyltransferases - genetics; tRNA Methyltransferases - metabolism; Yeasts - genetics; Yeasts - metabolism
• ISSN: 1355-8382; 1469-9001; 1469-9001
• DOI: 10.1261/rna.033654.112

The structural and functional integrity of tRNA is crucial for translation. In the yeast Saccharomyces cerevisiae , certain aberrant pre-tRNA species are subject to nuclear surveillance, leading to 3′ exonucleolytic degradation, and certain mature tRNA species are subject to rapid tRNA decay (RTD) if they are appropriately hypomodified or bear specific destabilizing mutations, leading to 5′-3′ exonucleolytic degradation by Rat1 and Xrn1. Thus, trm8 -Δ trm4 -Δ strains are temperature sensitive due to lack of m 7 G 46 and m 5 C and the consequent RTD of tRNA Val(AAC) , and tan1 -Δ trm44 -Δ strains are temperature sensitive due to lack of ac 4 C 12 and Um 44 and the consequent RTD of tRNA Ser(CGA) and tRNA Ser(UGA) . It is unknown how the RTD pathway interacts with translation and other cellular processes, and how generally this pathway acts on hypomodified tRNAs. We provide evidence here that elongation factor 1A (EF-1A) competes with the RTD pathway for substrate tRNAs, since its overexpression suppresses the tRNA degradation and the growth defect of strains subject to RTD, whereas reduced levels of EF-1A have the opposite effect. We also provide evidence that RTD acts on a variety of tRNAs lacking one or more different modifications, since trm1 -Δ trm4 -Δ mutants are subject to RTD of tRNA Ser(CGA) and tRNA Ser(UGA) due to lack of m 2,2 G 26 and m 5 C, and since trm8 -Δ, tan1 -Δ, and trm1 -Δ single mutants are each subject to RTD. These results demonstrate that RTD interacts with the translation machinery and acts widely on hypomodified tRNAs.