Alternative splicing modulation by G-quadruplexes.
Authors
Georgakopoulos-Soares, Ilias
Wong, Hei Yuen
Medhi, Ragini
Furlan, Giulia
Miska, Eric A
Kwok, Chun Kit
Publication Date
2022-05-03Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Nature Publishing Group UK
Volume
13
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Georgakopoulos-Soares, I., Parada, G. E., Wong, H. Y., Medhi, R., Furlan, G., Munita, R., Miska, E. A., et al. (2022). Alternative splicing modulation by G-quadruplexes.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-30071-7
Abstract
Alternative splicing is central to metazoan gene regulation, but the regulatory mechanisms are incompletely understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold near splice junctions. The importance of G4s in RNA is emphasised by a higher enrichment for the non-template strand. RNA-seq data from mouse and human neurons reveals an enrichment of G4s at exons that were skipped following depolarisation induced by potassium chloride. We validate the formation of stable RNA G4s for three candidate splice sites by circular dichroism spectroscopy, UV-melting and fluorescence measurements. Moreover, we find that sQTLs are enriched at G4s, and a minigene experiment provides further support for their role in promoting exon inclusion. Analysis of >1,800 high-throughput experiments reveals multiple RNA binding proteins associated with G4s. Finally, exploration of G4 motifs across eleven species shows strong enrichment at splice sites in mammals and birds, suggesting an evolutionary conserved splice regulatory mechanism.
Keywords
Article, /631/208/212/2019, /631/337/2019, /42/44, /45/77, /45/29, article
Identifiers
s41467-022-30071-7, 30071
External DOI: https://doi.org/10.1038/s41467-022-30071-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336829
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk