Talk on Friday 03:30-03:45pm submitted by Gina Nostramo
tRNA introns: A novel class of small non-coding regulatory RNAs
Regina Nostramo (Department of Molecular Genetics, The Ohio State University), Anita K. Hopper (Department of Molecular Genetics, The Ohio State University)
From archaea to humans, a subset of tRNA encoding genes possess introns. These introns are spliced out and rapidly degraded as part of the tRNA maturation process. tRNA intron splicing is essential in all studied eukaryotes because for at least one tRNA family, all reiterated tRNA genes contain an intron. Thus, the genome cannot be fully decoded without tRNA intron removal. This raises the intriguing question of why tRNA introns have been evolutionarily conserved. One possibility is that like many other components of tRNA biology that multitask with pathways for other RNAs (Hopper & Nostramo, 2019), the released introns may serve biological roles, functioning as small non-coding regulatory RNAs by interacting with mRNAs through sequence complementarity. To test this hypothesis, we first generated a strain lacking the tRNAIleUAU introns and assessed changes in mRNA levels of 32 ORFs with long stretches of complementarity to the intron, relative to wild-type cells. Absence of the tRNAIle introns elicited significant increases in mRNA levels for genes with intron complementarity as compared to ORFs without. Conversely, modest overexpression of the free tRNAIle intron elicited decreases in mRNA levels for genes with complementarity. These data suggest that tRNAIle introns function as inhibitors of sequence-specific gene expression/mRNA turnover. Extension of our analyses to the tRNATrpCCA intron supports these findings. Marked H2O2-induced increases in the tRNATrp intron elicited a decrease in ATG5 mRNA levels. However, this effect was abolished when complementarity between the intron and ATG5 mRNA was disrupted. Interestingly, evidence of an additional mechanism for the function of tRNA introns was also observed, in which tRNA introns can act as enhancers of translation. Overall, our data support the exciting possibility that tRNA introns are the newest member of non-coding regulatory RNAs and can function as both positive and negative regulators of gene expression.
Hopper AK and Nostramo R. (2019) tRNA Processing and Subcellular Trafficking Proteins Multitask in Pathways for Other RNAs. Front Genet. 10:96.
Keywords: tRNA, introns, gene expression