Repository logo

RNA G-quadruplex structures control ribosomal protein production

Published version

Change log


Varshney, Dhaval 
Cuesta, Sergio Martinez 
Herdy, Barbara 
Abdullah, Ummi Binti 
Tannahill, David 


Abstract: 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.


Funder: Herchel Smith Funds

Funder: Wellcome Trust; doi:

Funder: Cancer Research UK; doi:


Article, /631/337/574, /631/92/610, /631/92, article

Journal Title

Scientific Reports

Conference Name

Journal ISSN


Volume Title



Nature Publishing Group UK