A novel tRNA degradation pathway that acts on mature tRNA

Abstract

Under normal conditions, tRNA biosynthesis results in extremely stable species that are exquisitely adapted for their specific roles in translation. Newly transcribed tRNAs undergo multiple processing steps and several quality control checks before use in the cytoplasm. We recently provided evidence for a mechanism to examine the integrity of mature tRNAs in the yeast Saccharomyces cerevisiae, since mature tRNAVal(AAC) in a trm8‐Δ trm4‐Δ strain (lacking 7‐methyl‐guanosine and 5‐methyl‐cytidine) is rapidly degraded and deacylated upon shift to 37°C, resulting in a growth defect (Alexandrov et al., 2006, Mol. Cell 21:87–96).We have examined the components required for this tRNA degradation pathway as well as the generality of this pathway for different tRNA species and modifications. We find that degradation of tRNAVal(AAC) is mediated by Met22, as well as the 5′–3′ exonucleases Rat1 and Xrn1, which also have established roles in rRNA and snoRNA processing, and mRNA turnover. Furthermore, we find that this MET22‐dependent pathway mediates the degradation of at least three other tRNA species defective in other tRNA modifications. This evidence firmly establishes the existence of a pathway that monitors the integrity of mature tRNAs.Funded by NIH grants 5T32GM068411 and GM52347.