Alternative splicing modulation by G-quadruplexes

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Ilias Georgakopoulos-Soares
  • Guillermo E. Parada
  • Hei Yuen Wong
  • Ragini Medhi
  • Giulia Furlan
  • Roberto Munita
  • Eric A. Miska
  • Martin Hemberg

Detail(s)

Original languageEnglish
Article number2404
Journal / PublicationNature Communications
Volume13
Online published3 May 2022
Publication statusPublished - 2022

Link(s)

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.

Research Area(s)

Citation Format(s)

Alternative splicing modulation by G-quadruplexes. / Georgakopoulos-Soares, Ilias; Parada, Guillermo E.; Wong, Hei Yuen et al.
In: Nature Communications, Vol. 13, 2404, 2022.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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