tRNA Arg-Derived Fragments Can Serve as Arginine Donors for Protein Arginylation

摘要

Arginyltransferase ATE1 mediates posttranslational arginylation and plays key roles in multiple physiological processes. ATE1 utilizes arginyl (Arg)-tRNAArgas the donor of Arg, putting this reaction into a direct competition with the protein synthesis machinery. Here, we address the question of ATE1- Arg-tRNAArgspecificity as a potential mechanism enabling this competitionin?vivo. Usingin?vitroarginylation assays and Ate1 knockout models, we find that, in addition to full-length tRNA, ATE1 is also able to utilize short tRNAArgfragments that bear structural resemblance to tRNA-derived fragments (tRF), a recently discovered class of small regulatory non-coding RNAs with global emerging biological role. Ate1 knockout cells show a decrease in tRFArggeneration and a significant increase in the ratio of tRNAArg:tRFArgcompared with wild type, suggesting a functional link between tRFArgand arginylation. We propose that generation of physiologically important tRFs can serve as a switch between translation and protein arginylation.