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| http://purl.uniprot.org/citations/22684629 | http://www.w3.org/2000/01/rdf-schema#comment | "The molecular basis of cell signal-regulated alternative splicing at the 3' splice site remains largely unknown. We isolated a protein kinase A-responsive ribonucleic acid (RNA) element from a 3' splice site of the synaptosomal-associated protein 25 (Snap25) gene for forskolin-inhibited splicing during neuronal differentiation of rat pheochromocytoma PC12 cells. The element binds specifically to heterogeneous nuclear ribonucleo protein (hnRNP) K in a phosphatase-sensitive way, which directly competes with the U2 auxiliary factor U2AF65, an essential component of early spliceosomes. Transcripts with similarly localized hnRNP K target motifs upstream of alternative exons are enriched in genes often associated with neurological diseases. We show that such motifs upstream of the Runx1 exon 6 also bind hnRNP K, and importantly, hnRNP K is required for forskolin-induced repression of the exon. Interestingly, this exon encodes the peptide domain that determines the switch of the transcriptional repressor/activator activity of Runx1, a change known to be critical in specifying neuron lineages. Consistent with an important role of the target genes in neurons, knocking down hnRNP K severely disrupts forskolin-induced neurite growth. Thus, through hnRNP K, the neuronal differentiation stimulus forskolin targets a critical 3' splice site component of the splicing machinery to control alternative splicing of crucial genes. This also provides a regulated direct competitor of U2AF65 for cell signal control of 3' splice site usage."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.org/dc/terms/identifier | "doi:10.1093/nar/gks504"xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/author | "Feng D."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/author | "Xie J."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/author | "Cao W."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/author | "Lobo V.G."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/author | "Razanau A."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/name | "Nucleic Acids Res"xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/pages | "8059-8071"xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/title | "Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation."xsd:string |
| http://purl.uniprot.org/citations/22684629 | http://purl.uniprot.org/core/volume | "40"xsd:string |
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