title: New kid on the ID block: neural functions of the Nab2/ZC3H14 class of Cys₃His tandem zinc-finger polyadenosine RNA binding proteins.
abstract: Polyadenosine RNA binding proteins (Pabs) play critical roles in regulating the polyadenylation, nuclear export, stability, and translation of cellular RNAs. Although most Pabs are ubiquitously expressed and are thought to play general roles in post-transcriptional regulation, mutations in genes encoding these factors have been linked to tissue-specific diseases including muscular dystrophy and now intellectual disability (ID). Our recent work defined this connection to ID, as we showed that mutations in the gene encoding the ubiquitously expressed Cys3His tandem zinc-finger (ZnF) Pab, ZC3H14 (Zinc finger protein, CCCH-type, number 14) are associated with non-syndromic autosomal recessive intellectual disability (NS-ARID). This study provided a first link between defects in Pab function and a brain disorder, suggesting that ZC3H14 plays a required role in regulating RNAs in nervous system cells. Here we highlight key questions raised by our study of ZC3H14 and its ortholog in the fruit fly Drosophila melanogaster, dNab2, and comment on future approaches that could provide insights into the cellular and molecular roles of this class of zinc finger-containing Pabs. We propose a summary model depicting how ZC3H14-type Pabs might play particularly important roles in neuronal RNA metabolism.
authors.affiliation: Emory University School of Medicine, 615 Michael Street, Atlanta, GA  30322, United States.
authors.forename: Seth
authors.initials: S
authors.lastname: Kelly
authors.forename: Changhui
authors.initials: C
authors.lastname: Pak
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
authors.forename: Andreas
authors.initials: A
authors.lastname: Kuss
authors.forename: Anita H
authors.initials: AH
authors.lastname: Corbett
authors.forename: Kenneth
authors.initials: K
authors.lastname: Moberg
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D039102:Poly(A)-Binding Proteins; D017434:Protein Structure, Tertiary; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C578708:Nab2 protein, Drosophila; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; C522547:ZC3H14 protein, human