Pre-mRNA splicing in C. elegans
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ABSTRACT:
PROVIDER: PRJNA663456 | ENA |
REPOSITORIES: ENA
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Project description:To study pre-mRNA splicing function of the ubiquitin-like protein Hub1/UBL-5 in Caenorhabditis elegans. We have employed splicing-sensitive microarray expression profiling to examine the changes in pre-mRNA splicing. We collected wild-type and ubl-5 knock out worms at L3 stage and isolated total RNA. Which was reverse transcribed to double-stranded cDNA and cRNA was generated by in vitro transcription. The labeled cRNA samples were fragmented at 60°C and hybridized on to an Agilent Gene Expression Microarray. The data showed accumulation of intron- and outron containing transcripts in ubl-5 knockout worms in comparison to wild-type worms
2022-11-02 | GSE157943 | GEO
Project description:The conserved ubiquitin-like protein Hub1/UBL-5 associates with proteins non-covalently. In yeast and human cells, Hub1 promotes splicing of precursor mRNAs with weak introns and alternative splicing, however, its splicing function has remained elusive in multicellular organisms. We demonstrate the splicing function of Hub1/UBL-5 in the free-living nematode Caenorhabditis elegans. UBL-5 binds to the HIND-containing splicing factors Snu66/SART-1 and PRP-38 and associates with other spliceosomal proteins. Caenorhabditis elegans hub1/ubl-5 mutants die at the larval L3 stage, and show accumulation of intron- and outron-containing transcripts. The latter observation adds to UBL-5’s splicing function in trans-RNA splicing. UBL-5 complements splicing defects of hub1-knockout Schizosaccharomyces pombe, confirming its functional conservation. Thus, UBL-5 is important for C. elegans development and cis- and trans-RNA splicing.
2024-05-21 | PXD033914 | Pride
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:Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in its phosphatase-independent manner, and identify262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. Especially, the exon-2b exclusion of GOLGA2 contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors, Brefeldin A and Golgicide A. Given that many cancers lack PTEN expression, our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers.
2018-10-18 | PXD009681 | Pride
Project description:Here we examine the role of mRNA splicing in Caenorhabditis elegans RNAi. We find that viable null mutations in U1 and U2-snRNP-specific splicing factor genes cause defects in RNAi. The U1A orthologue rnp-2 is required for normal ERGO-1 Argonaute-class 26G siRNA biogenesis, trans-splicing of the eri-6/7 transcript and targeting of poorly conserved gene transcripts by WAGO Argonaute-class 22G siRNAs. We find that poorly spliced gene transcripts engaged by the siRNA generating machinery are poorly conserved, possess few introns, and often have introns that are divergent from introns found in highly conserved genes.
2018-05-28 | GSE113301 | GEO
Project description:RNA editing in nascent RNA affects pre-mRNA splicing
| PRJNA415378 | ENA
Project description:Disease modelling of core pre-mRNA splicing factor haploinsufficiency
| PRJNA532422 | ENA
Project description:Mutations in pre-mRNA processing factors (PRPFs) cause autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause retinal disease. We have generated transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well as Prpf31+/- mouse tissues, which revealed that disrupted alternative splicing occurred for specific splicing programmes. Mis-splicing of genes encoding pre-mRNA splicing proteins was limited to patient-specific retinal cells and Prpf31+/- mouse retinae and RPE. Mis-splicing of genes implicated in ciliogenesis and cellular adhesion was associated with severe RPE defects that include disrupted apical-basal polarity, reduced trans-epithelial resistance and phagocytic capacity, and decreased cilia length and incidence. Disrupted cilia morphology also occurred in patient-derived photoreceptors, associated with progressive degeneration and cellular stress. In situ gene-editing of a pathogenic mutation rescued protein expression and key cellular phenotypes in RPE and photoreceptors, providing proof-of-concept for future therapeutic strategies.
2018-08-20 | PXD010821 | Pride
Project description:Investigating the consequences of selection bias in analysis of pre-mRNA splicing
2023-05-03 | GSE160046 | GEO
Project description:The production of a mature mRNA in eukaryotes requires both transcription by RNA polymerase (pol) II and co-transcriptional processes, including mRNA capping, splicing, and cleavage and polyadenylation. The pol II complex serves as a hub to coordinate transcription and co-transcriptional processes, especially via the carboxyl terminal domain (CTD) of the large subunit of pol II that is composed in human of 52 repeats of the heptapeptide Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 and that can be modified by several post-translational modifications. To understand better the effects of pre-mRNA splicing on pol II transcription, we investigated the transcriptional effects of two small molecule inhibitors of splicing: Madrasin and Isoginkgetin. We found that while Madrasin can quickly inhibit pre-mRNA splicing, it is not the case of Isoginkgetin, which affects transcription before any visible effect on pre-mRNA splicing. Interestingly, we found that these two small molecules promote a global transcriptional readthrough, including intronless protein-coding genes and histone genes, which is not the case of the splicing inhibitors targeting the splicing factor SF3B1.
2024-08-20 | GSE221279 | GEO