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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing.

ABSTRACT: CDK11 phosphorylates SF3B1 and is essential for constitutive splicing.

PROVIDER: PRJNA770909 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16312803_1.fastq.gz	Fastqsanger.gz
	SRR16312803_2.fastq.gz	Fastqsanger.gz
	SRR16312804_1.fastq.gz	Fastqsanger.gz
	SRR16312804_2.fastq.gz	Fastqsanger.gz
	SRR16312805_1.fastq.gz	Fastqsanger.gz

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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (iCLIP)

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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (ChIP-seq)

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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (4sU-seq)

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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (RNA-seq)

Project description:CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (RNA-seq)

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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (iCLIP)

Project description:Pre-mRNA splicing is a highly regulated process catalyzing intron excision by spliceosome. Spliceosome activation is a major control step requiring dramatic protein and RNA rearrangements leading to a catalytically active complex. Prior research has linked hyperphosphorylation of SF3B1, a subunit of U2 snRNP, with spliceosome activation and catalytically active spliceosome, rendering a relevant kinase a key player for pre-mRNA splicing. Here we use OTS964, the first potent inhibitor of cyclin-dependent kinase 11 (CDK11), to show rapid and selective dephosphorylation of SF3B1 on threonines required for spliceosome activation. CDK11 associates with SF3B1 and its inhibition causes massive intron retention, block in precatalytic spliceosome complex B to activated spliceosome complex Bact transition and accumulation of non-functional spliceosomes on pre-mRNA and chromatin. These studies reveal crucial regulatory role of CDK11 in human pre-mRNA splicing and define the compound OTS964 as a quality chemical biology probe for CDK11.

2022-07-09 | GSE185811 | GEO

CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (ChIP-seq)

2022-07-09 | GSE185812 | GEO

CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (4sU-seq)

2022-07-09 | GSE185810 | GEO

CDK11 phosphorylates SF3B1 and is essential for constitutive splicing (RNA-seq)

2022-07-09 | GSE185809 | GEO

CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1

Project 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 via an ordered assembly of intermediate complexes. Spliceosome activation is a major control step requiring dramatic protein and RNA rearrangements leading to a catalytically active complex. Splicing factor 3B subunit 1 (SF3B1) protein, a subunit of the U2 snRNP, is phosphorylated during spliceosome activation, but the responsible kinase 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 association of SF3B1 with U5 and U6 snRNAs in spliceosome activated Bact complex and it can be blocked by OTS964, a potent and selective inhibitor of CDK11. CDK11 inhibition prevents spliceosomal transition from the precatalytic complex B to the activated complex Bact and leads to widespread intron retention and accumulation of non-functional spliceosomes on pre-mRNAs and chromatin. We characterize OTS964 as a quality chemical biology probe for CDK11 and demonstrate a central role of CDK11 in spliceosome assembly and splicing regulation.

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CDK11 phosphorylates SF3B1 and is essential for constitutive splicing.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-09 | GSE185813 | GEO