TRNA: Splicing and Intron Turnover and Possible Functions

Abstract

A subset of tRNA genes in eukaryotes contains an intron. tRNAs introns are short sequences located 1 nt. 3′ of the anticodon. Introns are removed from precursor tRNAs (pre-tRNA) by the conserved heterotetrameric tRNA splicing endonuclease (SEN), that recognizes pre-tRNA structure rather than sequence motifs at splice junctions. In vertebrate cells intron removal from pre-tRNAs occurs in the nucleoplasm; in contrast, pre-tRNA splicing in budding yeast and fission yeast occurs on the mitochondrial surface (Yoshihisa et al. 2003; Wan & Hopper, 2018); therefore, pre-tRNA splicing on the mitochondrial surface has been conserved for greater than 500 million years. Free tRNA introns are rarely detected in cells because they are rapidly and efficiently destroyed. We identified at least 5 separate, family-specific mechanisms that function in tRNA intron destruction (Wu & Hopper, 2014; Bao, Metcalf & Hopper, unpublished). Interestingly, under particular stress conditions, specific tRNA introns accumulate to high levels, possibly indicative of their functions in stress responses (Peltier, Metcalf, & Hopper, unpublished). Moreover, we discovered that tRNA introns possess long stretches of perfect complementarity to particular budding yeast mRNA ORFs (Bao, Nostramo, & Hopper, unpublished). Deletion of the introns from the 2 copies of the genes encoding tRNAIleUAU results in elevated levels of mRNAs with complementarity, but not mRNAs lacking complementarity; further, transformation of the cells lacking the tRNAIleUAU introns with extrachromosomal intron-containing tRNAIleUAU suppresses the mRNA enhanced levels. These results support the hypothesis that tRNA introns may function as a novel type of noncoding regulatory RNA, perhaps functioning in stress response (Nostramo & Hopper, unpublished).