CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082286" target="_blank" >RIV/00159816:_____/25:00082286 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/25:00143644

Result on the web

<a href="https://academic.oup.com/nar/article/53/22/gkaf1343/8402091" target="_blank" >https://academic.oup.com/nar/article/53/22/gkaf1343/8402091</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkaf1343" target="_blank" >10.1093/nar/gkaf1343</a>

Result language

angličtina

Original language name

CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing

Original language description

Cyclin-dependent kinase 11 (CDK11) is essential for the regulation of pre-mRNA splicing via phosphorylation of the core spliceosome component SF3B1. This phosphorylation is a marker of the catalytically active spliceosomes; thus, it is important to identify the mechanisms that regulate CDK11 itself. Here, we report that a small subset of CDK11 is phosphorylated on the activation T-loop threonine 595 (Thr595) and is associated with the activated spliceosome on chromatin in gene bodies. Mutational analyses revealed that Thr595 is essential for the formation of the active CDK11 complex with cyclin L and SAP30BP. CDK11 transiently associates with CDK7, a transcriptional kinase that also promotes the activation of other CDKs. Inhibition of CDK7 initially decreases transcription, but longer durations of inhibition lead to production of unspliced pre-mRNAs. The onset of the CDK7-mediated splicing defect correlates with the sequential dephosphorylation of CDK11 Thr595 and SF3B1. SILAC-based phosphoproteomics upon brief CDK11 inhibition identified SF3B1, CDC5L, and ESS2 as CDK11 substrates, which overlap with the previously identified CDK7 substrates in the spliceosome. In summary, our study suggests that CDK7 likely acts via CDK11 Thr595 phosphorylation to regulate pre-mRNA splicing in cells. The identification of additional CDK11 substrates points to its broader role in spliceosome regulation.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10603 - Genetics and heredity (medical genetics to be 3)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Volume of the periodical

53

Issue of the periodical within the volume

22

Country of publishing house

GB - UNITED KINGDOM

Number of pages

23

Pages from-to

nestránkováno

UT code for WoS article

001643965500001

EID of the result in the Scopus database

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