Defective escape behavior in DEAH-Box RNA Helicase mutants improved by restoring Glycine receptor expression

H Hirata; K Ogino; K Yamada; S Leacock; Robert J Harvey

doi:10.1523/JNEUROSCI.1157-13.2013

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Defective escape behavior in DEAH-Box RNA Helicase mutants improved by restoring Glycine receptor expression

Journal article

Open access

Peer reviewed

Defective escape behavior in DEAH-Box RNA Helicase mutants improved by restoring Glycine receptor expression

H Hirata, K Ogino, K Yamada, S Leacock and Robert J Harvey

Journal of Neuroscience, Vol.33(37), pp.14638-14644

2013

DOI: https://doi.org/10.1523/JNEUROSCI.1157-13.2013

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Abstract

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 encodingRNAhelicase Dhx37. In Dhx37 mutants, ribosomalRNAlevels were unchanged, whereas GlyRα1, α3, and α4a subunitmRNAlevels were decreased due to a splicing defect.Wefound that Dhx37 can interact with GlyRα1, α3, andα4a 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. © 2013 the authors.

Details

Title: Defective escape behavior in DEAH-Box RNA Helicase mutants improved by restoring Glycine receptor expression
Authors: H Hirata (Author) - National Institute of Genetics, Japan
K Ogino (Author) - National Institute of Genetics, Japan
K Yamada (Author) - National Institute of Genetics, Japan
S Leacock (Author) - University College London, United Kingdom
Robert J Harvey (Author) - University College London, United Kingdom
Publication details: Journal of Neuroscience, Vol.33(37), pp.14638-14644
Publisher: Society for Neuroscience (SFN)
Date published: 2013
DOI: 10.1523/JNEUROSCI.1157-13.2013
ISSN: 0270-6474
Copyright note: Copyright © 2013 Hirata et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450465002621
Output Type: Journal article

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Web Of Science research areas: Neurosciences

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