Alternative splicing modulation by G-quadruplexes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 05 2022
03 05 2022
Historique:
received:
23
07
2019
accepted:
30
03
2022
entrez:
3
5
2022
pubmed:
4
5
2022
medline:
6
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35504902
doi: 10.1038/s41467-022-30071-7
pii: 10.1038/s41467-022-30071-7
pmc: PMC9065059
doi:
Substances chimiques
RNA-Binding Proteins
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2404Subventions
Organisme : Cancer Research UK
ID : C13474/A18583
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C6946/A14492
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104640/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 092096/Z/10/Z
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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