2. Academic Validation
  3. Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2, impairs neural function in Drosophila and humans

Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2, impairs neural function in Drosophila and humans

  • Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12390-5. doi: 10.1073/pnas.1107103108.
Changhui Pak 1,  Masoud Garshasbi,  Kimia Kahrizi,  Christina Gross,  Luciano H Apponi,  John J Noto,  Seth M Kelly,  Sara W Leung,  Andreas Tzschach,  Farkhondeh Behjati,  Seyedeh Sedigheh Abedini,  Marzieh Mohseni,  Lars R Jensen,  Hao Hu,  Brenda Huang,  Sara N Stahley,  Guanglu Liu,  Kathryn R Williams,  Sharon Burdick,  Yue Feng,  Subhabrata Sanyal,  Gary J Bassell,  Hans-Hilger Ropers,  Hossein Najmabadi,  Anita H Corbett,  Kenneth H Moberg,  Andreas W Kuss
Affiliations

Affiliation

  • 1 Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
PMID: 21734151 DOI: 10.1073/pnas.1107103108
Abstract

Here we report a human intellectual disability disease locus on chromosome 14q31.3 corresponding to mutation of the ZC3H14 gene that encodes a conserved polyadenosine RNA binding protein. We identify ZC3H14 mRNA transcripts in the human central nervous system, and we find that rodent ZC3H14 protein is expressed in hippocampal neurons and colocalizes with poly(A) RNA in neuronal cell bodies. A Drosophila melanogaster model of this disease created by mutation of the gene encoding the ZC3H14 ortholog dNab2, which also binds polyadenosine RNA, reveals that dNab2 is essential for development and required in neurons for normal locomotion and flight. Biochemical and genetic data indicate that dNab2 restricts bulk poly(A) tail length in vivo, suggesting that this function may underlie its role in development and disease. These studies reveal a conserved requirement for ZC3H14/dNab2 in the metazoan nervous system and identify a poly(A) RNA binding protein associated with a human brain disorder.

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