Hirata, H., Ogino, K., Yamada, K., Leacock, S., and Harvey, R.J. (2013) Defective Escape Behavior in DEAH-Box RNA Helicase Mutants Improved by Restoring Glycine Receptor Expression. The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(37):14638-14644.
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, ribosomal RNA levels were unchanged, whereas GlyR α1, α3, and α4a subunit mRNA levels were decreased due to a splicing
defect. We found that Dhx37 can interact with GlyR α1, α3, and α4a transcripts but not with the GlyR α2 subunit mRNA. Overexpression
of GlyR α1, α3, or α4a subunits in Dhx37-deficient embryos restored normal behavior. Conversely, antisense-mediated knockdown
of multiple GlyR α 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 α subunit mRNAs, thereby regulating glycinergic
synaptic transmission and associated motor behaviors. To our knowledge, this is the first identification of pathologically
relevant substrates for an RNA helicase.