Journal article
Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts
Scientific reports, Vol.6(1), pp.30896-30896
08/03/2016
DOI: 10.1038/srep30896
PMCID: PMC4971515
PMID: 27485310
Abstract
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.
Details
- Title: Subtitle
- Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts
- Creators
- Sunil K. Verma - The University of Texas Medical Branch at GalvestonVaibhav Deshmukh - Baylor College of MedicineCurtis A. Nutter - The University of Texas Medical Branch at GalvestonElizabeth Jaworski - The University of Texas Medical Branch at GalvestonWenhao Jin - National University of SingaporeLalita Wadhwa - Baylor College of MedicineJoshua Abata - Pensacola Christian CollegeMarco Ricci - University of New MexicoJoy Lincoln - The Ohio State UniversityJames F. Martin - Texas Heart InstituteGene W. Yeo - University of California San DiegoMuge N. Kuyumcu-Martinez - The University of Texas Medical Branch at Galveston
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.6(1), pp.30896-30896
- DOI
- 10.1038/srep30896
- PMID
- 27485310
- PMCID
- PMC4971515
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- HG0046590; NS075449 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL091878 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) UL1TR001439 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) R01HG004659 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) UTMB 5FY12-21 / March of Dimes Starter Basil O'Connor Starter Scholar Award R01DE023177 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) R01NS075449 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 15GRNT22830010 / American Heart Association
- Language
- English
- Date published
- 08/03/2016
- Academic Unit
- Cardiothoracic Surgery
- Record Identifier
- 9984322808402771
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