Ontology highlight
ABSTRACT:
PROVIDER: PRJNA453385 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CUG-binding protein 1 (CUGBP1) and muscleblind-like 1 (MBNL1) are developmentally regulated RNA-binding proteins that are causally associated with myotonic dystrophy type 1. We extensively determined RNA-binding sites of CUGBP1 and MBNL1 to investigate their roles in RNA processing. We also analyzed polypyrimidine tract-binding protein (PTB) as a control. CUGBP1 and MBNL1 preferentially bind to alternatively spliced introns and exons, respectively, and regulate alternative splicing events. Moreover, CUGBP1 and MBNL1 are preferentially bound to the 3' untranslated regions (UTRs), in particular of genes for RNA-binding proteins, and facilitate decay of the bound mRNAs. In addition, CUGBP1 and MBNL1 mutually destabilize mRNA. Precise temporal regulation of CUGBP1 and MBNL1 are likely to be essential for accurate control of destabilization of a broad spectrum of genes as well as of alternative splicing events in cell differentiation and tissue development.
2012-01-04 | E-MTAB-414 | biostudies-arrayexpress
Project description:The vertebrate and neural-specific SR-related protein nSR100/SRRM4 regulates an extensive program of alternative splicing with critical roles in nervous system development. However, the mechanism by which nSR100 controls its target exons is poorly understood. We demonstrate that nSR100-dependent neural exons are associated with a unique configuration of intronic cis-elements that promote rapid switch-like regulation during neurogenesis. A key feature of this configuration is the insertion of specialized intronic enhancers between polypyrimidine tracts and acceptor sites that bind nSR100 to potently activate exon inclusion in neural cells, while weakening 3' splice site recognition and contributing to exon skipping in non-neural cells. nSR100 further operates by forming multiple interactions with early spliceosome components bound proximal to 3' splice sites. These multifaceted interactions achieve dominance over neural exon silencing mediated by the splicing regulator PTBP1. The results thus illuminate a widespread mechanism by which a critical neural exon network is activated during neurogenesis. RNA-Seq was used to obtain mRNA profiles of various N2A and 293T cell lines from human and mouse, respectively, to investigate the roles of nSR100, Ptbp1 and U2af65 in alternative splicing regulation. PAR-iCLIP and iCLIP experiments followed by high throughput sequencing were conducted to obtain RNA binding profiles of nSR100, PTBP1 and U2af65.
2014-09-11 | E-GEOD-57278 | biostudies-arrayexpress
Project description:The epithelial to mesenchymal transition (EMT) is an essential biological process during embryonic development and has also been implicated in cancer metastasis. Previous studies have characterized transcriptional regulation and key transcription factors that impact EMT. However, the role of alternative splicing (AS) regulation in EMT has only recently emerged and remains relatively uncharacterized. Here we used a robust in vitro EMT model to dynamically and comprehensively characterize splicing switches during EMT in a temporal manner.
2016-04-05 | GSE75487 | GEO
Project description:The mechanisms by which entire programs of gene regulation emerged during evolution are poorly understood. Neuronal microexons represent the most conserved class of alternative splicing in vertebrates and are critical for proper brain development and function. Here, we discover neural microexon programs in non-vertebrate species and trace their origin to bilaterian ancestors through the emergence of a previously uncharacterized ‘enhancer of microexons' (eMIC) protein domain. The eMIC domain originated as an alternative, neural-enriched splice isoform of the pan-eukaryotic Srrm2/SRm300 splicing factor gene, and subsequently became fixed in the vertebrate and neuronal-specific splicing regulator Srrm4/nSR100 and its paralog Srrm3. Remarkably, the eMIC domain is necessary and sufficient for microexon splicing, and functions by interacting with the earliest components required for exon recognition. The emergence of a novel domain with restricted expression in the nervous system thus resulted in the evolution of splicing programs that contributed to qualitatively expand neuronal molecular complexity in bilaterians.
2019-03-12 | PXD010034 | Pride
Project description:Precise temporal regulation of Dux is important for embryo development
| PRJNA556588 | ENA
Project description:Stem cells need to balance self-renewal and differentiation for correct tissue development and homeostasis. Defects in this balance can lead to developmental defects or tumor formation. In recent years, mRNA splicing has emerged as one important mechanism regulating cell fate decisions. Here we address the role of the evolutionary conserved splicing co-factor Barricade (Barc)/CUS2/Tat-SF1 in Drosophila neural stem cell (neuroblast) lineage formation. We show that Barc is required for the generation of neurons during Drosophila brain development by ensuring correct neural progenitor proliferation and differentiation. Barc associates with components of the U2 small nuclear ribonucleic proteins (snRNP), and its depletion causes alternative splicing in form of intron retention in a subset of genes. Using bioinformatics analysis and a cell culture based splicing assay, we found that Barc dependent introns share three major traits: they are short, GC rich and have weak 3’ splice sites. Our results show that Barc, together with the U2snRNP, plays an important role in regulating neural stem cell lineage progression during brain development and facilitates correct splicing of a subset of introns.
2017-11-02 | PXD006068 | Pride
Project description:We sequenced mRNA from mouse E14.5 embryonic cortex to compare gene expression level and alternative splicing events between 2 control (WT) and 2 Qk cKO. A set of tissue specific splicing factors are thought to govern alternative splicing events during neural progenitors (NPC) to neuron transition by regulating neuron specific exons. Here we proposed one such a factor, RNA-binding protein Qki5, which is specifically expressed in neural stem cells. We performed mRNAseq analysis by using mRNAs obtained from developing cerebral cortices in Qk conditional knockout (cKO) mice. Expectedly, we found huge numbers of alternative splicing changes between control and conditional knock-out relative to that of transcripts level changes. Furthermore, DAVID and Meta-scape analysis revealed that affected spliced genes are involved in axon-development and microtubule-based process. Among these, Ninein protein coding mRNA is listed as a Qk protein dependent alternative splicing targets. Interestingly, this exon encodes very long poly-peptides (2,121 nt) and is known as a previously defined dynamic RNA switch during NPC-to-neuron transition. In addition, we validated that the regulation of this large exon is consistent with Qki5 dependent alternative exon inclusion mode obtained from our previous Qki5 HITS-CLIP analysis. Together Qki5 will add to a list factor of alternative splicing in NPC-to-neuron transition.
2019-04-17 | GSE123927 | GEO
Project description:Alternative splicing (AS) plays a critical role in cell fate transitions, development and disease. Recent studies have shown that AS also influences pluripotency and somatic cell reprogramming. We profiled transcriptome-wide AS changes that occur during reprogramming of fibroblasts to pluripotency. This analysis revealed distinct phases of AS during reprogramming, including a splicing program that is unique to transgene-independent iPS cells. Changes in the expression of alternative splicing factors Zcchc24, Esrp1, Mbnl1/2 and Rbm47 were demonstrated to be key contributors to phase-specific AS. RNA binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS during reprogramming by different RNA binding proteins. Ectopic expression of Esrp1 enhanced reprogramming, in part by modulating the AS of the epithelial specific transcription factor Grhl1.These data represent a comprehensive temporal analysis of the dynamic regulation of AS during the acquisition of pluripotency. ES cells from 3 independent E3.5 blastocysts from either Control (Esrp1 WT/WT; Esrp2 -/-) or Esrp DKO (Esrp1 floxed/floxed; Esrp2 -/-) were transfected with pLVX-EGFP-Cre, puro selected and RNA was isolated 6 days later.
2016-03-15 | E-GEOD-76222 | biostudies-arrayexpress
Project description:Alternative splicing (AS) plays a critical role in cell fate transitions, development and disease. Recent studies have shown that AS also influences pluripotency and somatic cell reprogramming. We profiled transcriptome-wide AS changes that occur during reprogramming of fibroblasts to pluripotency. This analysis revealed distinct phases of AS during reprogramming, including a splicing program that is unique to transgene-independent iPS cells. Changes in the expression of alternative splicing factors Zcchc24, Esrp1, Mbnl1/2 and Rbm47 were demonstrated to be key contributors to phase-specific AS. RNA binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS during reprogramming by different RNA binding proteins. Ectopic expression of Esrp1 enhanced reprogramming, in part by modulating the AS of the epithelial specific transcription factor Grhl1.These data represent a comprehensive temporal analysis of the dynamic regulation of AS during the acquisition of pluripotency.
2016-03-15 | GSE70022 | GEO
Project description:Alternative splicing (AS) plays a critical role in cell fate transitions, development and disease. Recent studies have shown that AS also influences pluripotency and somatic cell reprogramming. We profiled transcriptome-wide AS changes that occur during reprogramming of fibroblasts to pluripotency. This analysis revealed distinct phases of AS during reprogramming, including a splicing program that is unique to transgene-independent iPS cells. Changes in the expression of alternative splicing factors Zcchc24, Esrp1, Mbnl1/2 and Rbm47 were demonstrated to be key contributors to phase-specific AS. RNA binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS during reprogramming by different RNA binding proteins. Ectopic expression of Esrp1 enhanced reprogramming, in part by modulating the AS of the epithelial specific transcription factor Grhl1.These data represent a comprehensive temporal analysis of the dynamic regulation of AS during the acquisition of pluripotency.
2016-03-15 | GSE76222 | GEO