Repository logo
 

Alternative splicing modulation by G-quadruplexes.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Georgakopoulos-Soares, Ilias 
Parada, Guillermo E  ORCID logo  https://orcid.org/0000-0003-1018-9882
Wong, Hei Yuen 
Medhi, Ragini 
Furlan, Giulia 

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.

Description

Keywords

Alternative Splicing, Animals, Exons, G-Quadruplexes, Mammals, Mice, RNA, RNA-Binding Proteins

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (092096/Z/10/Z, 104640/Z/14/Z)