TRNAArg-Derived Fragments Can Serve as Arginine Donors for Protein Arginylation. Issue 7 (16th July 2020)

• Record Type: Journal Article
• Authors: Avcilar-Kucukgoze, Irem; Gamper, Howard; Polte, Christine; Ignatova, Zoya; Kraetzner, Ralph; Shtutman, Michael; Hou, Ya-Ming; Dong, Dawei W.; Kashina, Anna
• Is Part Of: Cell chemical biology. Volume 27:Issue 7(2020)
• Page Start: 839
• Page End: 849.e4
• Publication Date: 2020-07-16
• Subjects: arginylation -- tRNA -- tRF; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2020.05.013
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: 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. Graphical Abstract: Highlights: ATE1-mediated arginylation is highly specific toward arginyl-tRNA Arg ATE1 selectively binds to tRNA and can utilize all mouse tRNA Arg species tRNA Arg -derived fragments can mediate arginylation ATE1 deletion alters the ratio of tRNA Arg to tRF Arg in cells Abstract : Avcilar-Kucukgoze et al. dissect the tRNA-dependent mechanisms of regulation of arginylation and suggest a role for tRNA-derived fragments, a type of small non-coding RNAs, in arginylation.