RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology
Ribosomes stalled during translation must be rescued to replenish the pool of translation-competent ribosomal subunits. Bacterial alternative rescue factor B (ArfB) releases nascent peptides from ribosomes stalled on mRNAs truncated at the A site, allowing ribosome recycling. Prior structural work revealed that ArfB recognizes such ribosomes by inserting its C-terminal alpha-helix into the vacant mRNA tunnel. In this work, we report that ArfB can efficiently recognize a wider range of mRNA substrates, including longer mRNAs that extend beyond the A-site codon. Single-particle cryo-EM unveils that ArfB employs two modes of function depending on the mRNA length. ArfB acts as a monomer to accommodate a shorter mRNA in the ribosomal A site. By contrast, longer mRNAs are displaced from the mRNA tunnel by more than 20 A and are stabilized in the intersubunit space by dimeric ArfB. Uncovering distinct modes of ArfB function resolves conflicting biochemical and structural studies, and may lead to re-examination of other ribosome rescue pathways, whose functions depend on mRNA lengths.
Ribosomal proteins, Ribosome, Structural biology
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DOI of Published Version
Carbone CE, Demo G, Madireddy R, Svidritskiy E, Korostelev AA. ArfB can displace mRNA to rescue stalled ribosomes. Nat Commun. 2020 Nov 3;11(1):5552. doi: 10.1038/s41467-020-19370-z. PMID: 33144582; PMCID: PMC7641280. Link to article on publisher's site
Carbone CE, Demo G, Madireddy R, Svidritskiy E, Korostelev AA. (2020). ArfB can displace mRNA to rescue stalled ribosomes. Open Access Publications by UMMS Authors. https://doi.org/10.1038/s41467-020-19370-z. Retrieved from https://escholarship.umassmed.edu/oapubs/4476
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This work is licensed under a Creative Commons Attribution 4.0 License.