ABSTRACT
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 remain largely unexplored. In a zebrafish mutagenesis screen to identify genes essential for heart development we identified a mutant that 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. Loss of ddx39ab hindered splicing of mRNAs encoding epigenetic regulatory factors, including members of the KMT2 gene family, leading to misregulation 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 the proper epigenetic status during differentiation of multiple cell lineages.
Footnotes
Author contributions
Conceptualization: I.C.S., X.L.; Validation: B.L.; Formal analysis: L.Z., Y.Y., B.L., X.L.; Investigation: L.Z., Y.Y., X.L.; Resources: Y.Y.; Data curation: L.Z., X.L.; Writing - original draft: X.L.; Writing - review & editing: I.C.S., X.L.; Visualization: L.Z., Y.Y., B.L.; Supervision: X.L.; Project administration: I.C.S., X.L.; Funding acquisition: I.C.S., X.L.
Funding
This research was funded, in part, by the National Natural Science Foundation of China (NSFC 31471354 and NSFC 31671505 to X.L.) and by the Natural Sciences and Engineering Research Council of Canada (RGPIN 2017-06502 to I.C.S.).
Data availability
RNA-seq data have been deposited at Gene Expression Omnibus under accession number GSE97067.
