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Author Notes:

Corresponding authors: E-mail acorbe2@emory.edu, E-mail kmoberg@emory.edu

We are most grateful to members of the Corbett and Moberg laboratories for helpful discussions and comments.

Subjects:

Research Funding:

This work was supported grants from the NIH to A.H.C. (GM058728) and K.H.M. (CA123368) and a Development Award from the MDA to A.B. (255856).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • BIOCHEMISTRY & MOLECULAR BIOLOGY
  • ZC3H14/ dNab2/ Nab2
  • polyadenosine RNA-binding protein
  • poly(A) tail
  • intellectual disability
  • MESSENGER-RNA
  • SYNAPTIC PLASTICITY
  • GENE-EXPRESSION
  • DROSOPHILA
  • NEURONS
  • DISEASE
  • POLYADENYLATION
  • NEUROTOXICITY
  • TRAFFICKING
  • RECOGNITION

A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14, in control of poly(A) tail length

Tools:

Journal Title:

RNA

Volume:

Volume 20, Number 5

Publisher:

, Pages 681-688

Type of Work:

Article | Final Publisher PDF

Abstract:

The ZC3H14 gene, which encodes a ubiquitously expressed, evolutionarily conserved, nuclear, zinc finger polyadenosine RNAbinding 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.

Copyright information:

© 2014 Kelly et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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