tRNA-Derived Fragments Can Serve as Arginine Donors for Protein Arginylation.
Irem Avcilar-Kucukgoze, Howard Gamper, Christine Polte, Zoya Ignatova, Ralph Kraetzner, Michael Shtutman, Ya-Ming Hou, Dawei W Dong, Anna Kashina
Author Information
Irem Avcilar-Kucukgoze: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Howard Gamper: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19144, USA.
Christine Polte: Institute of Biochemistry and Molecular Biology, University of Hamburg, 20148 Hamburg, Germany.
Zoya Ignatova: Institute of Biochemistry and Molecular Biology, University of Hamburg, 20148 Hamburg, Germany.
Ralph Kraetzner: Department of Pediatrics and Adolescent Medicine, University Medical Center G��ttingen, 37075 G��ttingen, Germany.
Michael Shtutman: Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Ya-Ming Hou: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19144, USA.
Dawei W Dong: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anna Kashina: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: akashina@upenn.edu.
Arginyltransferase ATE1 mediates posttranslational arginylation and plays key roles in multiple physiological processes. ATE1 utilizes arginyl (Arg)-tRNA 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 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 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 generation and a significant increase in the ratio of tRNA:tRF compared with wild type, suggesting a functional link between tRF and arginylation. We propose that generation of physiologically important tRFs can serve as a switch between translation and protein arginylation.
