CDK11 regulates pre-mRNA splicing by phosphorylation ofSF3B1
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00126884" target="_blank" >RIV/00216224:14740/22:00126884 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/22:00077674
Result on the web
<a href="https://www.nature.com/articles/s41586-022-05204-z" target="_blank" >https://www.nature.com/articles/s41586-022-05204-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41586-022-05204-z" target="_blank" >10.1038/s41586-022-05204-z</a>
Alternative languages
Result language
angličtina
Original language name
CDK11 regulates pre-mRNA splicing by phosphorylation ofSF3B1
Original language description
RNA splicing, the process of intron removal from pre-mRNA, is essential for the regulation of gene expression. It is controlled by the spliceosome, a megadalton RNA-protein complex that assembles de novo on each pre-mRNA intron through an ordered assembly of intermediate complexes(1,2). Spliceosome activation is a major control step that requires substantial protein and RNA rearrangements leading to a catalytically active complex(1-5). Splicing factor 3B subunit 1 (SF3B1) protein-a subunit of the U2 small nuclear ribonucleoprotein(6)-is phosphorylated during spliceosome activation(7-)(10), but the kinase that is responsible has not been identified. Here we show that cyclin-dependent kinase 11 (CDK11) associates with SF3B1 and phosphorylates threonine residues at its N terminus during spliceosome activation. The phosphorylation is important for the association between SF3B1 and U5 and U6 snRNAs in the activated spliceosome, termed the B(act )complex, and the phosphorylation can be blocked by OTS964, a potent and selective inhibitor of CDK11. Inhibition of CDK11 prevents spliceosomal transition from the precatalytic complex B to the activated complex B-act and leads to widespread intron retention and accumulation of non-functional spliceosomes on pre-mRNAs and chromatin. We demonstrate a central role of CDK11 in spliceosome assembly and splicing regulation and characterize OTS964 as a highly selective CDK11 inhibitor that suppresses spliceosome activation and splicing.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
NATURE
ISSN
0028-0836
e-ISSN
1476-4687
Volume of the periodical
609
Issue of the periodical within the volume
7928
Country of publishing house
DE - GERMANY
Number of pages
6
Pages from-to
829-834
UT code for WoS article
000854742900002
EID of the result in the Scopus database
2-s2.0-85138212060