Journal Article

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

Garshasbi, Masoud, Kahrizi, Kimia, Apponi, Luciano H, Huang, Brenda, Abedini, Seyedeh Sedigheh, Behjati, Farkhondeh, Kuss, Andreas W, Hu, Hao, Gross, Christina, Stahley, Sara N, Williams, Kathryn R, Corbett, Anita H, Feng, Yue, Tzschach, Andreas, Liu, Guanglu, Mohseni, Marzieh, Noto, John J, Moberg, Kenneth H, Kelly, Seth M, Bassell, Gary J, Sanyal, Subhabrata, Pak, ChangHui, Ropers, Hans-Hilger, Najmabadi, Hossein, Burdick, Sharon, Jensen, Lars R, Leung, Sara W

2011

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adolescent / Adult / Amino Acid Sequence / Animal models / Animals / Biological Sciences / Brain / Cell body / Central nervous system / Central Nervous System - physiology / chromosome 14 / Chromosome Mapping / Chromosomes, Human, Pair 14 - genetics / Cohort Studies / Consanguinity / Conserved Sequence / Data processing / disease models / Drosophila / Drosophila melanogaster / Drosophila melanogaster - genetics / Drosophila melanogaster - physiology / Drosophila Proteins - genetics / Drosophila Proteins - physiology / Evolution, Molecular / Female / Flight / Flight, Animal - physiology / Gene Knockdown Techniques / genes / Genes, Recessive / Genetic mutation / Hippocampus / Hippocampus - metabolism / Human genetics / Humans / Insects / Intellectual disability / Intellectual Disability - genetics / Iran / loci / Locomotion / Male / Mental retardation / Messenger RNA / Metazoa / Models, Animal / Molecular Sequence Data / Mutation / Nervous system / Neurons / Nuclear Proteins - genetics / Nuclear Proteins - physiology / Pedigree / Polyadenylation / Protein isoforms / Proteins / RNA / RNA binding proteins / RNA, Messenger - genetics / RNA, Messenger - metabolism / RNA-binding protein / RNA-Binding Proteins - genetics / RNA-Binding Proteins - physiology / rodents / Sequence Homology, Amino Acid / Young Adult / Zinc Fingers - genetics