| http://purl.uniprot.org/citations/23300487 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23300487 | http://www.w3.org/2000/01/rdf-schema#comment | "Facioscapulohumeral muscular dystrophy (FSHD) is a common muscle disease whose molecular pathogenesis remains largely unknown. Over-expression of FSHD region gene 1 (FRG1) in mice, frogs, and worms perturbs muscle development and causes FSHD-like phenotypes. FRG1 has been implicated in splicing, and we asked how splicing might be involved in FSHD by conducting a genome-wide analysis in FRG1 mice. We find that splicing perturbations parallel the responses of different muscles to FRG1 over-expression and disease progression. Interestingly, binding sites for the Rbfox family of splicing factors are over-represented in a subset of FRG1-affected splicing events. Rbfox1 knockdown, over-expression, and RNA-IP confirm that these are direct Rbfox1 targets. We find that FRG1 is associated to the Rbfox1 RNA and decreases its stability. Consistent with this, Rbfox1 expression is down-regulated in mice and cells over-expressing FRG1 as well as in FSHD patients. Among the genes affected is Calpain 3, which is mutated in limb girdle muscular dystrophy, a disease phenotypically similar to FSHD. In FRG1 mice and FSHD patients, the Calpain 3 isoform lacking exon 6 (Capn3 E6-) is increased. Finally, Rbfox1 knockdown and over-expression of Capn3 E6-inhibit muscle differentiation. Collectively, our results suggest that a component of FSHD pathogenesis may arise by over-expression of FRG1, reducing Rbfox1 levels and leading to aberrant expression of an altered Calpain 3 protein through dysregulated splicing."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1003186"xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Ares M. Jr."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Shiue L."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Gabellini D."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Bortolanza S."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Neguembor M.V."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Pistoni M."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Xynos A."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/author | "Cline M.S."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/pages | "e1003186"xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/title | "Rbfox1 downregulation and altered calpain 3 splicing by FRG1 in a mouse model of Facioscapulohumeral muscular dystrophy (FSHD)."xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/23300487 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23300487 |
| http://purl.uniprot.org/citations/23300487 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23300487 |
| http://purl.uniprot.org/uniprot/Q9JJ43#attribution-663EBC2B7ED2B087B49E5DE36B6C41FB | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23300487 |
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| http://purl.uniprot.org/uniprot/#_A0A1Q1NN66-mappedCitation-23300487 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23300487 |
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| http://purl.uniprot.org/uniprot/#_A0A1Q1PRS6-mappedCitation-23300487 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23300487 |