RGD Reference Report - Rbm20 regulates titin alternative splicing as a splicing repressor. - Rat Genome Database

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Rbm20 regulates titin alternative splicing as a splicing repressor.

Authors: Li, Shijun  Guo, Wei  Dewey, Colin N  Greaser, Marion L 
Citation: Li S, etal., Nucleic Acids Res. 2013 Feb 1;41(4):2659-72. doi: 10.1093/nar/gks1362. Epub 2013 Jan 9.
RGD ID: 152025504
Pubmed: PMID:23307558   (View Abstract at PubMed)
PMCID: PMC3575840   (View Article at PubMed Central)
DOI: DOI:10.1093/nar/gks1362   (Journal Full-text)

Titin, a sarcomeric protein expressed primarily in striated muscles, is responsible for maintaining the structure and biomechanical properties of muscle cells. Cardiac titin undergoes developmental size reduction from 3.7 megadaltons in neonates to primarily 2.97 megadaltons in the adult. This size reduction results from gradually increased exon skipping between exons 50 and 219 of titin mRNA. Our previous study reported that Rbm20 is the splicing factor responsible for this process. In this work, we investigated its molecular mechanism. We demonstrate that Rbm20 mediates exon skipping by binding to titin pre-mRNA to repress the splicing of some regions; the exons/introns in these Rbm20-repressed regions are ultimately skipped. Rbm20 was also found to mediate intron retention and exon shuffling. The two Rbm20 speckles found in nuclei from muscle tissues were identified as aggregates of Rbm20 protein on the partially processed titin pre-mRNAs. Cooperative repression and alternative 3' splice site selection were found to be used by Rbm20 to skip different subsets of titin exons, and the splicing pathway selected depended on the ratio of Rbm20 to other splicing factors that vary with tissue type and developmental age.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rbm20Ratheart formation involved_inIDA PMID:23307558UniProt 
Rbm20Ratnegative regulation of mRNA splicing, via spliceosome involved_inIDA PMID:23307558UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rbm20Ratnucleus is_active_inIDA PMID:23307558UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Rbm20  (RNA binding motif protein 20)


Additional Information