RNA G-quadruplex structures control ribosomal protein production

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 vi...

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Autores principales:	Dhaval Varshney, Sergio Martinez Cuesta, Barbara Herdy, Ummi Binti Abdullah, David Tannahill, Shankar Balasubramanian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/74c8d5eda01043c79eff0b1eba8756f2
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spelling	oai:doaj.org-article:74c8d5eda01043c79eff0b1eba8756f22021-11-28T12:20:13ZRNA G-quadruplex structures control ribosomal protein production10.1038/s41598-021-01847-62045-2322https://doaj.org/article/74c8d5eda01043c79eff0b1eba8756f22021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01847-6https://doaj.org/toc/2045-2322Abstract 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.Dhaval VarshneySergio Martinez CuestaBarbara HerdyUmmi Binti AbdullahDavid TannahillShankar BalasubramanianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dhaval Varshney Sergio Martinez Cuesta Barbara Herdy Ummi Binti Abdullah David Tannahill Shankar Balasubramanian RNA G-quadruplex structures control ribosomal protein production
description	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.
format	article
author	Dhaval Varshney Sergio Martinez Cuesta Barbara Herdy Ummi Binti Abdullah David Tannahill Shankar Balasubramanian
author_facet	Dhaval Varshney Sergio Martinez Cuesta Barbara Herdy Ummi Binti Abdullah David Tannahill Shankar Balasubramanian
author_sort	Dhaval Varshney
title	RNA G-quadruplex structures control ribosomal protein production
title_short	RNA G-quadruplex structures control ribosomal protein production
title_full	RNA G-quadruplex structures control ribosomal protein production
title_fullStr	RNA G-quadruplex structures control ribosomal protein production
title_full_unstemmed	RNA G-quadruplex structures control ribosomal protein production
title_sort	rna g-quadruplex structures control ribosomal protein production
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/74c8d5eda01043c79eff0b1eba8756f2
work_keys_str_mv	AT dhavalvarshney rnagquadruplexstructurescontrolribosomalproteinproduction AT sergiomartinezcuesta rnagquadruplexstructurescontrolribosomalproteinproduction AT barbaraherdy rnagquadruplexstructurescontrolribosomalproteinproduction AT ummibintiabdullah rnagquadruplexstructurescontrolribosomalproteinproduction AT davidtannahill rnagquadruplexstructurescontrolribosomalproteinproduction AT shankarbalasubramanian rnagquadruplexstructurescontrolribosomalproteinproduction
_version_	1718408024192712704

RNA G-quadruplex structures control ribosomal protein production

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