Alternative splicing modulation by G-quadruplexes
(2022) In Nature Communications 13(1).- 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... (More)
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.
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- author
- Georgakopoulos-Soares, Ilias ; Parada, Guillermo E. ; Wong, Hei Yuen ; Medhi, Ragini ; Furlan, Giulia ; Munita, Roberto LU ; Miska, Eric A. ; Kwok, Chun Kit and Hemberg, Martin
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 2404
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:35504902
- scopus:85129303989
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-022-30071-7
- language
- English
- LU publication?
- yes
- id
- a4c1416c-bccd-48ad-9a00-c291f068f8e9
- date added to LUP
- 2022-07-05 14:51:03
- date last changed
- 2024-04-16 14:10:52
@article{a4c1416c-bccd-48ad-9a00-c291f068f8e9, abstract = {{<p>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.</p>}}, author = {{Georgakopoulos-Soares, Ilias and Parada, Guillermo E. and Wong, Hei Yuen and Medhi, Ragini and Furlan, Giulia and Munita, Roberto and Miska, Eric A. and Kwok, Chun Kit and Hemberg, Martin}}, issn = {{2041-1723}}, language = {{eng}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Alternative splicing modulation by G-quadruplexes}}, url = {{http://dx.doi.org/10.1038/s41467-022-30071-7}}, doi = {{10.1038/s41467-022-30071-7}}, volume = {{13}}, year = {{2022}}, }