RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism including RNA synthesis, processing and degradation. The function and mechanism of action of most of these helicases in animal development and human disease are largely unexplored. In a zebrafish mutagenesis screen to identify genes essential for heart development we identified a mutant which disrupts the gene encoding the RNA helicase DEAD-box 39ab (ddx39ab). Homozygous ddx39ab mutant embryos exhibit profound cardiac and trunk muscle dystrophy, along with lens abnormalities, caused by abrupt terminal differentiation of cardiomyocyte, myoblast and lens fiber cells. Further investigation indicated that loss of ddx39ab hindered mRNA splicing of members of the kmt2 gene family, leading to mis-regulation of structural gene expression in cardiomyocyte, myoblast and lens fiber cells. Taken together, these results show that Ddx39ab plays an essential role in establishment of proper epigenetic status during differentiation of multiple cell lineages.
The DEAD box RNA helicase Ddx39ab is essential for myocyte and lens development in zebrafish
These authors contributed equally to this work.
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