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.
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.
Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Joshua M
JM
Dewe
Joseph M
JM
Whipple
Irina
I
Chernyakov
Laura N
LN
Jaramillo
Eric M
EM
Phizicky
D001667:Binding, Competitive / Q000502:physiology; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D050505:Mutant Proteins / Q000378:metabolism / Q000502:physiology; D030781:Organisms, Genetically Modified; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics / Q000502:physiology*; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013379:Substrate Specificity; D014162:Transfection; D015003:Yeasts / Q000235:genetics / Q000378:metabolism; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism
D050505:Mutant Proteins; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D029701:Saccharomyces cerevisiae Proteins; C410826:TEF1 protein, S cerevisiae; C057183:TEF2 protein, S cerevisiae; D012343:RNA, Transfer; D012359:tRNA Methyltransferases