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Broken heart: disruption of the RNA binding protein rbm24a alters heart morphogenesis and leads to cardiomyopathy
Author(s) -
Brastrom Lindy,
Slusarski Diane
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02211
Subject(s) - heart development , zebrafish , myh6 , cardiomyopathy , biology , microbiology and biotechnology , gene knockdown , rna , heart failure , medicine , rna binding protein , alternative splicing , morpholino , cardiology , genetics , gene , messenger rna , gene isoform , myh7 , embryonic stem cell
Congenital heart disease is the most common birth defect in the United States. While transcriptional control of heart development has been well studied, only recently has post‐transcriptional control started to be appreciated. One mechanism of post‐transcriptional control is through RNA regulation. RNA binding proteins are a class of proteins which regulate RNA through various mechanisms including polyadenylation, stability, and splicing. Recently, the RNA binding protein, rbm24a , has been linked as a key regulator of heart development. Depletion of rbm24a in our model, the zebrafish, leads to cardiomyopathy and cardiac edema. We hypothesize rbm24a plays a key role in atrial development. Utilizing both morpholino knockdown and CRISPR/Cas9 mutagenesis, we find cardiomyopathy and cardiac edema in rbm24a depleted animals. To understand the underlying mechanism of the heart defect, we started by examining the formation of the heart tube. While the heart tube successfully forms and jogs to the left side of the body, the size of the heart tube is comparable to control animals at 12 hours post fertilization (hpf) but is significantly smaller by 24hpf. Previous research has shown the mouse ortholog of rbm24a , Rbm24 , binds directly to the atrial‐specific gene Myh6 . This suggests the first steps of heart development occur normally with the cardiomyopathy potentially arising from a defect in atrial development. We are currently exploring the possibilities that the atrium has (1) fewer cells and (2) that the decrease in atrium cell number is due to a migration, proliferation, apoptosis, and/or differentiation defect. Here, we explore the mechanism(s) by which the RNA binding protein, rbm24a , is leading to cardiomyopathy and cardiac edema in zebrafish.