title: A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14, in control of poly(A) tail length.
abstract: The ZC3H14 gene, which encodes a ubiquitously expressed, evolutionarily conserved, nuclear, zinc finger polyadenosine RNA-binding protein, was recently linked to autosomal recessive, nonsyndromic intellectual disability. Although studies have been carried out to examine the function of putative orthologs of ZC3H14 in Saccharomyces cerevisiae, where the protein is termed Nab2, and Drosophila, where the protein has been designated dNab2, little is known about the function of mammalian ZC3H14. Work from both budding yeast and flies implicates Nab2/dNab2 in poly(A) tail length control, while a role in poly(A) RNA export from the nucleus has been reported only for budding yeast. Here we provide the first functional characterization of ZC3H14. Analysis of ZC3H14 function in a neuronal cell line as well as in vivo complementation studies in a Drosophila model identify a role for ZC3H14 in proper control of poly(A) tail length in neuronal cells. Furthermore, we show here that human ZC3H14 can functionally substitute for dNab2 in fly neurons and can rescue defects in development and locomotion that are present in dNab2 null flies. These rescue experiments provide evidence that this zinc finger-containing class of nuclear polyadenosine RNA-binding proteins plays an evolutionarily conserved role in controlling the length of the poly(A) tail in neurons.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Kelly
authors.forename: Sara W
authors.initials: SW
authors.lastname: Leung
authors.forename: ChangHui
authors.initials: C
authors.lastname: Pak
authors.forename: Ayan
authors.initials: A
authors.lastname: Banerjee
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Moberg
authors.forename: Anita H
authors.initials: AH
authors.lastname: Corbett
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C578708:Nab2 protein, Drosophila; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C522547:ZC3H14 protein, human
keywords: ZC3H14/dNab2/Nab2; intellectual disability; poly(A) tail; polyadenosine RNA-binding protein