RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology
Frameshifting 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.
Molecular Biology, mRNA, ribosomes
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DOI of Published Version
bioRxiv 2020.12.29.424751; doi: https://doi.org/10.1101/2020.12.29.424751. Link to preprint on bioRxiv.
Demo G, Loveland AB, Svidritskiy E, Gamper HB, Hou Y, Korostelev AA. (2020). Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.12.29.424751. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1867
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