RGD Reference Report - Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts. - Rat Genome Database

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Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.

Authors: Verma, Sunil K  Deshmukh, Vaibhav  Nutter, Curtis A  Jaworski, Elizabeth  Jin, Wenhao  Wadhwa, Lalita  Abata, Joshua  Ricci, Marco  Lincoln, Joy  Martin, James F  Yeo, Gene W  Kuyumcu-Martinez, Muge N 
Citation: Verma SK, etal., Sci Rep. 2016 Aug 3;6:30896. doi: 10.1038/srep30896.
RGD ID: 329848956
Pubmed: PMID:27485310   (View Abstract at PubMed)
PMCID: PMC4971515   (View Article at PubMed Central)
DOI: DOI:10.1038/srep30896   (Journal Full-text)

Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart failure. Genome-wide transcriptome changes have been identified at early stages in the right ventricle (RV) of infants with HLHS, although the molecular mechanisms remain unknown. Here, we demonstrate that the RNA binding protein Rbfox2, which is mutated in HLHS patients, is a contributor to transcriptome changes in HLHS patient RVs. Our results indicate that majority of transcripts differentially expressed in HLHS patient hearts have validated Rbfox2 binding sites. We show that Rbfox2 regulates mRNA levels of targets with 3'UTR binding sites contributing to aberrant gene expression in HLHS patients. Strikingly, the Rbfox2 nonsense mutation identified in HLHS patients truncates the protein, impairs its subcellular distribution and adversely affects its function in RNA metabolism. Overall, our findings uncover a novel role for Rbfox2 in controlling transcriptome in HLHS.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RBFOX2Humanhypoplastic left heart syndrome  IEP protein:alternative form:heart (human)RGD 
Rbfox2Rathypoplastic left heart syndrome  ISORBFOX2 (Homo sapiens)protein:alternative form:heart (human)RGD 
Rbfox2Mousehypoplastic left heart syndrome  ISORBFOX2 (Homo sapiens)protein:alternative form:heart (human)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rbfox2Ratcytoplasm  IDA  RGD 
Rbfox2Ratnucleus  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rbfox2  (RNA binding fox-1 homolog 2)

Genes (Mus musculus)
Rbfox2  (RNA binding protein, fox-1 homolog (C. elegans) 2)

Genes (Homo sapiens)
RBFOX2  (RNA binding fox-1 homolog 2)


Additional Information