To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes.

Autor: Grove DJ; The Ohio State Biochemistry Program, Department of Biological Chemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA., Russell PJ; The Ohio State Biochemistry Program, Department of Biological Chemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.; The Cellular, Molecular, Biochemical Sciences Program, Department of Biological Chemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA., Kearse MG; The Ohio State Biochemistry Program, Department of Biological Chemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.; The Cellular, Molecular, Biochemical Sciences Program, Department of Biological Chemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: Wiley interdisciplinary reviews. RNA [Wiley Interdiscip Rev RNA] 2024 Mar-Apr; Vol. 15 (2), pp. e1833.
DOI: 10.1002/wrna.1833
Abstrakt: Selection of the correct start codon is critical for high-fidelity protein synthesis. In eukaryotes, this is typically governed by a multitude of initiation factors (eIFs), including eIF2·GTP that directly delivers the initiator tRNA (Met-tRNA i Met ) to the P site of the ribosome. However, numerous reports, some dating back to the early 1970s, have described other initiation factors having high affinity for the initiator tRNA and the ability of delivering it to the ribosome, which has provided a foundation for further work demonstrating non-canonical initiation mechanisms using alternative initiation factors. Here we provide a critical analysis of current understanding of eIF2A, eIF2D, and the MCT-1·DENR dimer, the evidence surrounding their ability to initiate translation, their implications in human disease, and lay out important key questions for the field. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Mechanisms Translation > Regulation.
(© 2024 The Authors. WIREs RNA published by Wiley Periodicals LLC.)
Databáze: MEDLINE