Demo, GabrielLoveland, Anna B.Svidritskiy, EgorGamper, Howard B.Hou, Ya-MingKorostelev, Andrei A.2022-08-232022-08-232020-12-292021-01-20<p>bioRxiv 2020.12.29.424751; doi: https://doi.org/10.1101/2020.12.29.424751. <a href="https://doi.org/10.1101/2020.12.29.424751" target="_blank" title="preprint on bioRxiv">Link to preprint on bioRxiv.</a></p>10.1101/2020.12.29.424751https://hdl.handle.net/20.500.14038/29651Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. Where and how in the elongation cycle +1-frameshifting occurs remains poorly understood. We captured six ∼3.5-Å-resolution cryo-EM structures of ribosomal elongation complexes formed with the GTPase elongation factor G (EF-G). Three 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, the tRNA shifts to the +1-frame codon near the P site, whereas the freed mRNA base bulges between the P and E sites and stacks 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 mRNA translocation.en-USThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.http://creativecommons.org/licenses/by-nc-nd/4.0/Molecular BiologymRNAribosomesMolecular BiologyNucleic Acids, Nucleotides, and NucleosidesStructural BiologyPreprinthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2896&amp;context=faculty_pubs&amp;unstamped=1https://escholarship.umassmed.edu/faculty_pubs/186721185464faculty_pubs/1867