SRI-41315 is a small molecule that enhances premature read-through of the stop codon by triggering the degradation of the translation termination factor eRF1. Cryo-EM structures and biochemical analyses reveal how SRI-41315 acts as a molecular glue between eRF1 and the decoding center of ribosomes, leading to increased recognition of the cryptic stop codon and eRF1 degradation.
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References
Hellen, C. U. T. Translation termination and ribosome recycling in eukaryotes. Cold Spring Harb. Perspect. Biol. 10, a032656 (2018). A review article describing translation termination.
Spelier, S., van Doorn, E. P. M., van der Ent, C. K., Beekman, J. M. & Koppens, M. A. J. Readthrough compounds for nonsense mutations: bridging the translational gap. Trends Mol. Med. 29, 297–314 (2023). This review article descripes therapeutic strategies for diseases caused by nonsense mutations.
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This is a summary of: Coelho, J. L. et al. The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center. Nat. Chem. Biol. https://doi.org/10.1038/s41589-023-01521-0 (2024).
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A molecular glue degrader of eRF1 on the ribosome. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-023-01522-z
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DOI: https://doi.org/10.1038/s41589-023-01522-z
