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dc.contributor.authorGeorgakopoulos-Soares, Ilias
dc.contributor.authorParada, Guillermo E
dc.contributor.authorWong, Hei Yuen
dc.contributor.authorMedhi, Ragini
dc.contributor.authorFurlan, Giulia
dc.contributor.authorMunita, Roberto
dc.contributor.authorMiska, Eric A
dc.contributor.authorKwok, Chun Kit
dc.contributor.authorHemberg, Martin
dc.date.accessioned2022-06-07T08:13:47Z
dc.date.available2022-06-07T08:13:47Z
dc.date.issued2022-05-03
dc.identifier.issn2041-1723
dc.identifier.other35504902
dc.identifier.otherPMC9065059
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337800
dc.description.abstractAlternative 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.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101528555
dc.sourceessn: 2041-1723
dc.subjectAnimals
dc.subjectMammals
dc.subjectMice
dc.subjectRNA-Binding Proteins
dc.subjectRNA
dc.subjectAlternative Splicing
dc.subjectExons
dc.subjectG-Quadruplexes
dc.titleAlternative splicing modulation by G-quadruplexes.
dc.typeArticle
dc.date.updated2022-06-07T08:13:47Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.85209
dcterms.dateAccepted2022-03-30
rioxxterms.versionofrecord10.1038/s41467-022-30071-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidParada, Guillermo E [0000-0003-1018-9882]
dc.contributor.orcidMunita, Roberto [0000-0002-6605-7160]
dc.contributor.orcidHemberg, Martin [0000-0001-8895-5239]
dc.identifier.eissn2041-1723
pubs.funder-project-idWellcome Trust (092096/Z/10/Z, 104640/Z/14/Z)
cam.issuedOnline2022-05-03


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International