RGD Reference Report - RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. - Rat Genome Database

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RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.

Authors: Guo, W  Schafer, S  Greaser, ML  Radke, MH  Liss, M  Govindarajan, T  Maatz, H  Schulz, H  Li, S  Parrish, AM  Dauksaite, V  Vakeel, P  Klaassen, S  Gerull, B  Thierfelder, L  Regitz-Zagrosek, V  Hacker, TA  Saupe, KW  Dec, GW  Ellinor, PT  MacRae, CA  Spallek, B  Fischer, R  Perrot, A  Ozcelik, C  Saar, K  Hubner, N  Gotthardt, M 
Citation: Guo W, etal., Nat Med. 2012 May;18(5):766-73. doi: 10.1038/nm.2693.
RGD ID: 7241566
Pubmed: PMID:22466703   (View Abstract at PubMed)
PMCID: PMC3569865   (View Article at PubMed Central)
DOI: DOI:10.1038/nm.2693   (Journal Full-text)

Alternative splicing has a major role in cardiac adaptive responses, as exemplified by the isoform switch of the sarcomeric protein titin, which adjusts ventricular filling. By positional cloning using a previously characterized rat strain with altered titin mRNA splicing, we identified a loss-of-function mutation in the gene encoding RNA binding motif protein 20 (Rbm20) as the underlying cause of pathological titin isoform expression. The phenotype of Rbm20-deficient rats resembled the pathology seen in individuals with dilated cardiomyopathy caused by RBM20 mutations. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20-dependent regulation of alternative splicing. In addition to titin (TTN), we identified a set of 30 genes with conserved splicing regulation between humans and rats. This network is enriched for genes that have previously been linked to cardiomyopathy, ion homeostasis and sarcomere biology. Our studies emphasize the key role of post-transcriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RBM20Humandilated cardiomyopathy  IAGP  RGD 
Rbm20Ratdilated cardiomyopathy  ISORBM20 (Homo sapiens) RGD 
Rbm20Mousedilated cardiomyopathy  ISORBM20 (Homo sapiens) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rbm20Ratheart formation involved_inIMP PMID:22466703UniProt 
Rbm20Ratregulation of RNA splicing involved_inIMP PMID:22466703UniProt 

Objects Annotated

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

Genes (Mus musculus)
Rbm20  (RNA binding motif protein 20)

Genes (Homo sapiens)
RBM20  (RNA binding motif protein 20)

Objects referenced in this article
Strain (SDxF344)F1-Rbm20m1Mlgw+/+ null Rattus norvegicus
Strain (SDxF344)F1-Rbm20m1Mlgw null Rattus norvegicus
Strain (SDxF344)F1xBN-Rbm20m1Mlgw+/+ null Rattus norvegicus
Strain (SDxF344)F1xBN-Rbm20m1Mlgw null Rattus norvegicus
Gene Rbm20m1Mlgw RNA binding motif protein 20; mutation 1, Marion Greaser Rattus norvegicus

Additional Information