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

Arginyltransferase ATE1 mediates posttranslational arginylation and plays key roles in multiple physiological processes. ATE1 utilizes arginyl (Arg)-tRNA^Arg as the donor of Arg, putting this reaction into a direct competition with the protein synthesis machinery. Here, we address the question of ATE1- Arg-tRNA^Arg specificity as a potential mechanism enabling this competition in vivo. Using in vitro arginylation assays and Ate1 knockout models, we find that, in addition to full-length tRNA, ATE1 is also able to utilize short tRNA^Arg fragments 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 tRF^Arg generation and a significant increase in the ratio of tRNA^Arg:tRF^Arg compared with wild type, suggesting a functional link between tRF^Arg and arginylation. We propose that generation of physiologically important tRFs can serve as a switch between translation and protein arginylation.