RGD Reference Report - A Splicing-Independent Function of RBM10 Controls Specific 3' UTR Processing to Regulate Cardiac Hypertrophy. - Rat Genome Database

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A Splicing-Independent Function of RBM10 Controls Specific 3' UTR Processing to Regulate Cardiac Hypertrophy.

Authors: Mohan, Nimmy  Kumar, Vikas  Kandala, Divya T  Kartha, Chandrasekharan C  Laishram, Rakesh S 
Citation: Mohan N, etal., Cell Rep. 2018 Sep 25;24(13):3539-3553. doi: 10.1016/j.celrep.2018.08.077.
RGD ID: 151667449
Pubmed: PMID:30257214   (View Abstract at PubMed)
DOI: DOI:10.1016/j.celrep.2018.08.077   (Journal Full-text)

RNA binding motif protein 10 (RBM10) is a regulator of alternative splicing in apoptosis and inflammation. We discovered a splicing-independent function of RBM10 critical for the regulation of heart failure (HF). RBM10 is enriched in the heart and associates with Star-PAP (TUT1) to control the expression and 3' end processing of cardiac mRNAs. The RBM10 RRM2 domain binds the Star-PAP catalytic domain, which directs Star-PAP activity toward polyadenylation. RBM10 binds the pre-mRNA UTR, assembles the Star-PAP complex, and guides this complex specifically to mRNAs encoding anti-hypertrophy regulators. Accordingly, we tested cellular hypertrophy in rat cardiomyoblasts and cardiac hypertrophy (CH) and the subsequent progression to HF in Wistar rat hearts. We demonstrated downregulation of RBM10 during CH and HF. Ectopic re-expression of RBM10 rescued cardiomyocyte hypertrophy. RBM10 depletion evoked a hypertrophic response in H9c2 cells. Our results establish an anti-hypertrophy mechanism mediated by RBM10 in the heart that is directly linked to HF.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RBM10HumanCardiomegaly  ISORbm10 (Rattus norvegicus)protein:decreased expression:heartRGD 
Rbm10RatCardiomegaly  IEP protein:decreased expression:heartRGD 
Rbm10MouseCardiomegaly  ISORbm10 (Rattus norvegicus)protein:decreased expression:heartRGD 
RBM10Humancongestive heart failure  ISORbm10 (Rattus norvegicus)protein:decreased expression:heartRGD 
Rbm10Ratcongestive heart failure  IEP protein:decreased expression:heartRGD 
Rbm10Mousecongestive heart failure  ISORbm10 (Rattus norvegicus)protein:decreased expression:heartRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rbm10Ratnegative regulation of cell growth involved in cardiac muscle cell development  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rbm10  (RNA binding motif protein 10)

Genes (Mus musculus)
Rbm10  (RNA binding motif protein 10)

Genes (Homo sapiens)
RBM10  (RNA binding motif protein 10)


Additional Information