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dc.contributor.author
Farberov, Luba
dc.contributor.author
Weissglas-Volkov, Daphna
dc.contributor.author
Shapira, Guy
dc.contributor.author
Zoabi, Yazeed
dc.contributor.author
Schiff, Chen
dc.contributor.author
Kloeckner-Gruissem, Barbara
dc.contributor.author
Neidhardt, John
dc.contributor.author
Shomron, Noam
dc.date.accessioned
2023-09-18T06:36:34Z
dc.date.available
2023-09-16T03:16:35Z
dc.date.available
2023-09-18T06:36:34Z
dc.date.issued
2023-10-20
dc.identifier.issn
2589-0042
dc.identifier.other
10.1016/j.isci.2023.107723
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/631810
dc.identifier.doi
10.3929/ethz-b-000631810
dc.description.abstract
Splicing of transcripts is catalyzed by the spliceosome, a mega-complex consisting of hundreds of proteins and five snRNAs, which employs direct interactions. When U1 snRNA forms high-affinity binding, namely more than eight base pairs, with the 5′SS, the result is usually a suppressing effect on the splicing activity. This likely occurs due to the inefficient unwinding of U1/5′SS base-pairing or other regulatory obstructions. Here, we show in vitro and in patient-derived cell lines that pre-microRNAs can modulate the splicing reaction by interacting with U1 snRNA. This leads to reduced binding affinity to the 5′SS, and hence promotes the inclusion of exons containing 5′SS, despite sequence-based high affinity to U1. Application of the mechanism resulted in correction of the splicing defect in the disease-causing VCAN gene from an individual with Wagner syndrome. This pre-miRNA/U1 interaction can regulate the expression of alternatively spliced exons, thus extending the scope of mechanisms regulating splicing.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Cell Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title
mRNA splicing is modulated by intronic microRNAs
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2023-08-28
ethz.journal.title
iScience
ethz.journal.volume
26
en_US
ethz.journal.issue
10
en_US
ethz.pages.start
107723
en_US
ethz.size
14 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Amsterdam
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2023-09-16T03:16:35Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2023-09-18T06:36:35Z
ethz.rosetta.lastUpdated
2024-02-03T03:35:01Z
ethz.rosetta.versionExported
true
ethz.COinS
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