Motor Neural Circuit Laboratory • Hirata Group

RNA helicases regulate RNA metabolism, but their substrate specificity and in vivo function remain largely unknown. We isolated spontaneous mutant zebrafish that exhibit an abnormal dorsal bend at the beginning of tactile-evoked escape swimming. Similar behavioral defects were observed in zebrafish embryos treated with strychnine, which blocks glycine receptors (GlyRs), suggesting that the abnormal motor response in mutants may be attributable to a deficit in glycinergic synaptic transmission. We identified a missense mutation in the gene encoding RNA helicase Dhx37. In Dhx37 mutants, GlyR alpha subunit mRNA levels were decreased due to a splicing defect. Overexpression of GlyR alpha subunits in Dhx37-deficient embryos restored normal behavior. Conversely, antisense knockdown of multiple GlyR alpha subunits in wild-type embryos was required to recapitulate the Dhx37 mutant phenotype. These results indicate that Dhx37 is specifically required for the biogenesis of a subset of GlyR alpha subunit mRNAs, thereby regulating glycinergic synaptic transmission and associated motor behaviors.