非表示:
キーワード:
Adolescent; Adult; Amino Acid Sequence; Animals; Central Nervous System/physiology; Chromosome Mapping; Chromosomes, Human, Pair 14/genetics; Cohort Studies; Consanguinity; Conserved Sequence; Drosophila Proteins/*genetics/*physiology; Drosophila melanogaster/genetics/physiology; Evolution, Molecular; Female; Flight, Animal/physiology; Gene Knockdown Techniques; Genes, Recessive; Hippocampus/metabolism; Humans; Intellectual Disability/*genetics; Iran; Male; Models, Animal; Molecular Sequence Data; *Mutation; Nuclear Proteins/*genetics/*physiology; Pedigree; RNA, Messenger/genetics/metabolism; RNA-Binding Proteins/*genetics/*physiology; Sequence Homology, Amino Acid; Young Adult; Zinc Fingers/genetics
要旨:
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.
