Similar Datasets
Project description:Analysis of the pre-mRNA splicing in the wild type
| PRJNA530755 | ENA
Project description:Analysis of atsf1-2 mutant seedlings for pre-mRNA splicing defect. The atsf1-2 mutant is a homozygous T-DNA insertion line isolated from a SALK line, SALK_062177. Results identify transcripts with altered alternative splicing pattern in the atsf1-2 mutant. We used microarrays to examine the transcriptome profile in the atsf1-2 mutant and identified genes of which transcript levels were changed significantly.
2014-03-31 | GSE48114 | GEO
Project description:Analysis of atsf1-2 mutant seedlings for pre-mRNA splicing defect. The atsf1-2 mutant is a homozygous T-DNA insertion line isolated from a SALK line, SALK_062177. Results identify transcripts with altered alternative splicing pattern in the atsf1-2 mutant. We used microarrays to examine the transcriptome profile in the atsf1-2 mutant and identified genes of which transcript levels were changed significantly. Arabidopsis seedlings were grown for 9 days under long day condition. They were then used for RNA extraction and hybridization on Affymetrix ATH1 Genome Array. Three replicates for Col-0 (control) and atsf1-2 (mutant) were compared respectively.
2014-03-31 | E-GEOD-48114 | biostudies-arrayexpress
Project description:pre-mRNA splicing in C. elegans
| PRJNA663456 | ENA
Project description:Cyclin-dependent kinase 11 (CDK11) is essential for the regulation of pre-mRNA splicing by phosphorylating SF3B1, a core spliceosome component. This phosphorylation is a marker of the catalytically active spliceosome, so it is important to identify the mechanisms that regulate CDK11. Herein, 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. The time course of the inhibition of CDK7 initially decreases transcription, but later produces unspliced pre-mRNAs. The dynamics of onset of the CDK7-mediated splicing defect correlates with the sequential dephosphorylation of CDK11 Thr595 and SF3B1. SILAC-based phospho-proteomics upon brief CDK11 inhibition identified SF3B1, CDC5L and ESS2 as CDK11 substrates, an 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 indicates its more complex role in spliceosome regulation.
2025-12-31 | GSE290846 | GEO
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
Project description:Mutants of tumor suppressor p53 not only lose the activity in genome stabilizing and in tumor suppression, but also exhibit oncogenic function in cancer cells. Most efforts in restoring p53 biological activity focus on either altering mutant-protein conformation or introducing an exogenous p53 gene into cells to eliminate p53-mutant cancer cells. Being different from these, we report that ceramide can restore the expression of wild-type p53 and induce p53-dependent apoptosis in deletion-mutant cancer cells. We show that endogenous long-carbon chain ceramide species (C16- to C24-ceramides) and exogenous C6-ceramide, rather than other sphingolipids, restore wild-type mRNA (intact exon-5), phosphorylated protein (Ser15 in exon-5) of p53, and p53-responsive proteins, including p21 and Bax, in ovarian cancer cells, which predominantly express a deleted exon-5 of p53 mutant before treatments. Consequently, the restored p53 sensitizes these p53-mutant cancer cells to DNA damage-induced growth arrest and apoptosis. Furthermore, we elucidate that ceramide activates protein phosphatase-1, and then the dephosphorylated serine/arginine-rich splicing-factor 1 (SRSF1) is translocated to the nucleus, thus promoting pre-mRNA splicing preferentially to wild-type p53 expression. These findings disclose an unrecognized mechanism that pre-mRNA splicing dysfunction can result in p53 deletion-mutants. Ceramide through SRSF1 restores wild-type p53 expression versus deletion-mutant and leads cancer cells to apoptosis. This suggests that heterozygous deletion-mutants of p53 can be restored in posttranscriptional level by using epigenetic approaches.
| S-EPMC4188706 | biostudies-literature
Project description:Measurement of expression levels as a time course after shifting temperature-sensitive splicing factor mutant cells from 23C to 37C. Analysis of WT SS330, prp17 null, prp17-1 and prp22-1 cells. Samples were analyzed at 0, 5, 15, 30, 60 and 120 min. Keywords = pre-mRNA splicing Keywords = time course Keywords = intron Keywords: time-course
2004-09-25 | GSE1784 | GEO
Project description:CDK7 regulates pre-mRNA splicing via CDK11
| PRJNA1230229 | ENA
Project 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.
2025-12-29 | PXD062535 | Pride