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

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

PROVIDER: PRJNA770913 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16312819.fastq.gz	Fastqsanger.gz
	SRR16312820.fastq.gz	Fastqsanger.gz
	SRR16312821.fastq.gz	Fastqsanger.gz
	SRR16312822.fastq.gz	Fastqsanger.gz
	SRR16312823.fastq.gz	Fastqsanger.gz

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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.

Project description:CDK11 phosphorylates SF3B1 and is essential for constitutive splicing.

| PRJNA770909 | ENA

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

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

| PRJNA770912 | ENA

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

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

| PRJNA770914 | ENA

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

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

| PRJNA770915 | ENA

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.

2022-07-09 | MSV000089855 | MassIVE

CDK11 is required for transcription of replication-dependent histone genes

Project description:Replication-dependent histones (RDH) are required for packaging of newly synthetized DNA into nucleosomes during the S phase when their expression is highly upregulated. However, the mechanisms of this upregulation in metazoan cells remain poorly understood. Using iCLIP and ChIP–seq, we found that human cyclin-dependent kinase 11 (CDK11) associates with RNA and chromatin of RDH genes primarily in the S phase. Moreover, its amino-terminal region binds FLASH, RDH-specific 3′-end processing factor, which keeps the kinase on the chromatin. CDK11 phosphorylates serine 2 (Ser2) of the carboxy-terminal domain of RNA polymerase II (RNAPII), which is initiated at the middle of RDH genes and is required for further RNAPII elongation and 3′-end processing. CDK11 depletion leads to decreased number of cells in S phase, likely owing to the function of CDK11 in RDH gene expression. Thus, the reliance of RDH expression on CDK11 could explain why CDK11 is essential for the growth of many cancers.

2020-04-28 | GSE118051 | GEO

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