Detailed Information on Publication Record
2022
CDK11 regulates pre-mRNA splicing by phosphorylation ofSF3B1
HLUCHÝ, Milan, Pavla GAJDUŠKOVÁ, Igor RUIZ DE LOS MOZOS, Michal RÁJECKÝ, Michael KLUGE et. al.Basic information
Original name
CDK11 regulates pre-mRNA splicing by phosphorylation ofSF3B1
Authors
HLUCHÝ, Milan (703 Slovakia, belonging to the institution), Pavla GAJDUŠKOVÁ (203 Czech Republic, belonging to the institution), Igor RUIZ DE LOS MOZOS, Michal RÁJECKÝ (203 Czech Republic, belonging to the institution), Michael KLUGE, Benedict-Tilman BERGER, Zuzana SLABÁ (703 Slovakia, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Elena WEISS, Jernej ULE, Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution), Stefan KNAPP, Kamil PARUCH (203 Czech Republic, belonging to the institution), Caroline C. FRIEDEL and Dalibor BLAŽEK (203 Czech Republic, guarantor, belonging to the institution)
Edition
NATURE, ENGLAND, NATURE PORTFOLIO, 2022, 0028-0836
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10608 Biochemistry and molecular biology
Country of publisher
Germany
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 64.800
RIV identification code
RIV/00216224:14740/22:00126884
Organization unit
Central European Institute of Technology
UT WoS
000854742900002
Keywords in English
Chromatin; Cyclin-Dependent Kinases; Phosphorylation; Ribonucleoprotein; U2 Small Nuclear; RNA Precursors; RNA Splicing; RNA Splicing Factors; Spliceosomes; Threonine
Tags
International impact, Reviewed
Změněno: 5/4/2023 10:42, Mgr. Pavla Foltynová, Ph.D.
Abstract
V originále
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.
Links
| CZ.1.05/1.1.00/02.0068, interní kód MU |
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| ED1.1.00/02.0068, research and development project |
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| EF16_025/0007381, research and development project |
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| GA21-19266S, research and development project |
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| LM2018127, research and development project |
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| LM2018130, research and development project |
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| MUNI/G/1129/2021, interní kód MU |
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