RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences
Biochemistry, Biophysics, and Structural Biology | Enzymes and Coenzymes | Nucleic Acids, Nucleotides, and Nucleosides
Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. How and where in the elongation cycle +1-frameshifting occurs remains poorly understood. We describe seven ~3.5-A-resolution cryo-EM structures of 70S ribosome complexes, allowing visualization of elongation and translocation by the GTPase elongation factor G (EF-G). Four structures with a + 1-frameshifting-prone mRNA reveal that frameshifting takes place during translocation of tRNA and mRNA. Prior to EF-G binding, the pre-translocation complex features an in-frame tRNA-mRNA pairing in the A site. In the partially translocated structure with EF-G*GDPCP, the tRNA shifts to the +1-frame near the P site, rendering the freed mRNA base to bulge between the P and E sites and to stack on the 16S rRNA nucleotide G926. The ribosome remains frameshifted in the nearly post-translocation state. Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during tRNA-mRNA translocation.
Rights and Permissions
Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Demo G, Gamper HB, Loveland AB, Masuda I, Carbone CE, Svidritskiy E, Hou YM, Korostelev AA. Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation. Nat Commun. 2021 Jul 30;12(1):4644. doi: 10.1038/s41467-021-24911-1. PMID: 34330903; PMCID: PMC8324841. Link to article on publisher's site
Demo G, Gamper HB, Loveland AB, Masuda I, Carbone CE, Svidritskiy E, Hou Y, Korostelev AA. (2021). Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation. Open Access Publications by UMass Chan Authors. https://doi.org/10.1038/s41467-021-24911-1. Retrieved from https://escholarship.umassmed.edu/oapubs/4856
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.