title: Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2, impairs neural function in Drosophila and humans.
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.
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Changhui
authors: C
authors: Pak
authors: Masoud
authors: M
authors: Garshasbi
authors: Kimia
authors: K
authors: Kahrizi
authors: Christina
authors: C
authors: Gross
authors: Luciano H
authors: LH
authors: Apponi
authors: John J
authors: JJ
authors: Noto
authors: Seth M
authors: SM
authors: Kelly
authors: Sara W
authors: SW
authors: Leung
authors: Andreas
authors: A
authors: Tzschach
authors: Farkhondeh
authors: F
authors: Behjati
authors: Seyedeh Sedigheh
authors: SS
authors: Abedini
authors: Marzieh
authors: M
authors: Mohseni
authors: Lars R
authors: LR
authors: Jensen
authors: Hao
authors: H
authors: Hu
authors: Brenda
authors: B
authors: Huang
authors: Sara N
authors: SN
authors: Stahley
authors: Guanglu
authors: G
authors: Liu
authors: Kathryn R
authors: KR
authors: Williams
authors: Sharon
authors: S
authors: Burdick
authors: Yue
authors: Y
authors: Feng
authors: Subhabrata
authors: S
authors: Sanyal
authors: Gary J
authors: GJ
authors: Bassell
authors: Hans-Hilger
authors: HH
authors: Ropers
authors: Hossein
authors: H
authors: Najmabadi
authors: Anita H
authors: AH
authors: Corbett
authors: Kenneth H
authors: KH
authors: Moberg
authors: Andreas W
authors: AW
authors: Kuss
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000502:physiology; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D015331:Cohort Studies; D003241:Consanguinity; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D005260:Female; D005426:Flight, Animal / Q000502:physiology; D055785:Gene Knockdown Techniques; D005808:Genes, Recessive; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007492:Iran; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D010375:Pedigree; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D055815:Young Adult; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C522547:ZC3H14 protein, human