Journal
JOURNAL OF NEUROSCIENCE
Volume 33, Issue 37, Pages 14638-14644Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1157-13.2013
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [23115719, 25920008]
- Takeda Science Foundation
- Action Medical Research
- Action Medical Research [1966] Funding Source: researchfish
- Medical Research Council [MR/J004049/1, G0601585, G0500833] Funding Source: researchfish
- MRC [MR/J004049/1, G0500833, G0601585] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [25920008] Funding Source: KAKEN
Ask authors/readers for more resources
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 alpha 1, alpha 3, and alpha 4a subunit mRNA levels were decreased due to a splicing defect. We found that Dhx37 can interact with GlyR alpha 1, alpha 3, and alpha 4a transcripts but not with the GlyR alpha 2 subunit mRNA. Overexpression of GlyR alpha 1, alpha 3, or alpha 4a subunits in Dhx37-deficient embryos restored normal behavior. Conversely, antisense-mediated 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. To our knowledge, this is the first identification of pathologically relevant substrates for an RNA helicase.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available