RNA G-quadruplex structures control ribosomal protein production.
Cuesta, Sergio Martinez
Abdullah, Ummi Binti
Springer Science and Business Media LLC
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Varshney, D., Cuesta, S. M., Herdy, B., Abdullah, U. B., Tannahill, D., & Balasubramanian, S. (2021). RNA G-quadruplex structures control ribosomal protein production.. Sci Rep https://doi.org/10.1038/s41598-021-01847-6
Four-stranded G-quadruplex (G4) structures form from guanine-rich tracts, but the extent of their formation in cellular RNA and details of their role in RNA biology remain poorly defined. Herein, we first delineate the presence of endogenous RNA G4s in the human cytoplasmic transcriptome via the binding sites of G4-interacting proteins, DDX3X (previously published), DHX36 and GRSF1. We demonstrate that a sub-population of these RNA G4s are reliably detected as folded structures in cross-linked cellular lysates using the G4 structure-specific antibody BG4. The 5' UTRs of protein coding mRNAs show significant enrichment in folded RNA G4s, particularly those for ribosomal proteins. Mutational disruption of G4s in ribosomal protein UTRs alleviates translation in vitro, whereas in cells, depletion of G4-resolving helicases or treatment with G4-stabilising small molecules inhibit the translation of ribosomal protein mRNAs. Our findings point to a common mode for translational co-regulation mediated by G4 structures. The results reveal a potential avenue for therapeutic intervention in diseases with dysregulated translation, such as cancer.
ERC Herchel Smith Funds
Cancer Research UK (CB4330)
Cancer Research UK (C9681/A29214)
European Research Council (339778)
Wellcome Trust (209441/Z/17/Z)
External DOI: https://doi.org/10.1038/s41598-021-01847-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330260
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