Stress promotes RNA G-quadruplex folding in human cells

Prakash Kharel, Marta Fay, Ekaterina V. Manasova, Paul J. Anderson, Alexander V. Kurkin, Junjie U. Guo () and Pavel Ivanov ()
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Prakash Kharel: Brigham and Women’s Hospital, Harvard Medical School
Marta Fay: Brigham and Women’s Hospital, Harvard Medical School
Ekaterina V. Manasova: Chemistry Department of Lomonosov Moscow State University
Paul J. Anderson: Brigham and Women’s Hospital, Harvard Medical School
Alexander V. Kurkin: Chemistry Department of Lomonosov Moscow State University
Junjie U. Guo: Yale School of Medicine
Pavel Ivanov: Brigham and Women’s Hospital, Harvard Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract Guanine (G)-rich nucleic acids can fold into G-quadruplex (G4) structures under permissive conditions. Although many RNAs contain sequences that fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. In this report, we showed that the folding of putative rG4s in human cells into rG4 structures is dynamically regulated under stress. By using high-throughput dimethylsulfate (DMS) probing, we identified hundreds of endogenous stress-induced rG4s, and validated them by using an rG4 pull-down approach. Our results demonstrate that stress-induced rG4s are enriched in mRNA 3′-untranslated regions and enhance mRNA stability. Furthermore, stress-induced rG4 folding is readily reversible upon stress removal. In summary, our study revealed the dynamic regulation of rG4 folding in human cells and suggested that widespread rG4 motifs may have a global regulatory impact on mRNA stability and cellular stress response.

Date: 2023
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DOI: 10.1038/s41467-023-35811-x

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