Novel cross talk between tRNA and mRNA processes exerted by Aminoacyl tRNA synthetases

Recent RNA interactome studies had identified many novel mRNA-binding proteins. Interestingly, a recurring family of proteins detected in these studies are the cytosolic aminoacyl tRNA synthetases (aaRSs). Association of this well-studied tRNA binding protein-family with mRNA raises intriguing questions regarding their possible targets, mode of interaction and the physiological significance of their dual interaction with tRNA and mRNA. We therefore investigated the repertoire of mRNAs bound by members of this family in yeast. Using RNA immunoprecipitation followed by deep sequencing (RIP-seq), we identified subsets of mRNAs associated with aaRSs. Interestingly, in all cases we observed strong association of each aaRS with its own mRNA (‘self-association’). We aimed to determine the target mRNA motif bound by a representative aaRS and identified that association occurs through its cognate tRNA anticodon-mimic. Point mutations within the anticodon-mimic dramatically reduces self-association, concomitant with increased translation, suggesting that self-association autoregulates translation. Finally, we found that overexpression of the cognate tRNA alleviates mRNA association and increases protein production in an anticodon-mimic dependent manner. Overall, our study reveals a novel aaRS-dependent cross talk between tRNA and mRNA processes that affects aaRS translation in response to amino-acid charging demands. Furthermore, it emphasizes the importance of interactions through similar RNA elements to coordinate distinct cellular processes.