Hsf1 is essential for proteotoxic stress response in smyd1b‐deficient embryos and fish survival under heat shock

Molecular chaperones play critical roles in post-translational maintenance in protein homeostasis. Previous studies have shown that loss of Smyd1b function results in defective myofibril organization and dramatic upregulation of heat shock protein gene (hsp) expression in muscle cells of zebrafish embryos. To investigate the molecular mechanisms and functional importance of this stress response, we characterized changes of gene expression in smyd1b knockdown and knockout embryos using RNA-seq. The results showed that the top upregulated genes encode mostly cytosolic heat shock proteins. Co-IP assay revealed that the upregulated cytosolic Hsp70s associate with myosin chaperone UNC45b which is critical for myosin protein folding and sarcomere assembly. Strikingly, several hsp70 genes also display muscle-specific upregulation in response to heat shock-induced stress in zebrafish embryos. To investigate the regulation of hsp gene upregulation and its functional significance in muscle cells, we generated heat shock factor 1 (hsf