Functions of unconventional mammalian translational GTPases GTPBP1 and GTPBP2

Genes Dev. 2018 Sep 1;32(17-18):1226-1241. doi: 10.1101/gad.314724.118. Epub 2018 Aug 14.

Abstract

GTP-binding protein 1 (GTPBP1) and GTPBP2 comprise a divergent group of translational GTPases with obscure functions, which are most closely related to eEF1A, eRF3, and Hbs1. Although recent reports implicated GTPBPs in mRNA surveillance and ribosome-associated quality control, how they perform these functions remains unknown. Here, we demonstrate that GTPBP1 possesses eEF1A-like elongation activity, delivering cognate aminoacyl-transfer RNA (aa-tRNA) to the ribosomal A site in a GTP-dependent manner. It also stimulates exosomal degradation of mRNAs in elongation complexes. The kinetics of GTPBP1-mediated elongation argues against its functioning in elongation per se but supports involvement in mRNA surveillance. Thus, GTP hydrolysis by GTPBP1 is not followed by rapid peptide bond formation, suggesting that after hydrolysis, GTPBP1 retains aa-tRNA, delaying its accommodation in the A site. In physiological settings, this would cause ribosome stalling, enabling GTPBP1 to elicit quality control programs; e.g., by recruiting the exosome. GTPBP1 can also deliver deacylated tRNA to the A site, indicating that it might function via interaction with deacylated tRNA, which accumulates during stresses. Although GTPBP2's binding to GTP was stimulated by Phe-tRNAPhe, suggesting that its function might also involve interaction with aa-tRNA, GTPBP2 lacked elongation activity and did not stimulate exosomal degradation, indicating that GTPBP1 and GTPBP2 have different functions.

Keywords: 80S ribosome; GTPBP1; GTPBP2; RNA exosome; trGTPase; translation elongation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exosome Multienzyme Ribonuclease Complex / metabolism
  • GTP Phosphohydrolases / metabolism
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • HEK293 Cells
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism*
  • Peptide Chain Elongation, Translational*
  • RNA Stability
  • RNA, Messenger / metabolism
  • RNA, Transfer / metabolism

Substances

  • RNA, Messenger
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • RNA, Transfer
  • Exosome Multienzyme Ribonuclease Complex
  • GTP Phosphohydrolases
  • GTPBP2 protein, human
  • GTPBP1 protein, human
  • Monomeric GTP-Binding Proteins