Document Detail


Modulation of neuritogenesis by a protein implicated in X-linked mental retardation.
MedLine Citation:
PMID:  19812318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Posttranscriptional regulation is an important control mechanism governing gene expression in neurons. We recently demonstrated that VCX-A, a protein implicated in X-linked mental retardation, is an RNA-binding protein that specifically binds the 5' end of capped mRNAs to prevent their decapping and decay. Previously, expression of VCX-A was reported to be testes restricted. Consistent with a role in cognitive function, we demonstrate that VCX-A is ubiquitously expressed in human tissues including the brain. Moreover, retinoic acid-induced differentiation of human SH-SY5Y neuroblastoma cells promoted the accumulation of VCX-A in distinct cytoplasmic foci within neurites that colocalize with staufen1-containing RNA granules, suggesting a role in translational suppression and/or mRNA transport. Exogenous expression of VCX-A in rat primary hippocampal neurons, which normally do not express the primate-restricted VCX proteins, promoted neurite arborization, and shRNA-directed knockdown of the VCX genes in SH-SY5Y cells resulted in a reduction of both primary and secondary neurite projections upon differentiation. We propose that the cap-binding property of VCX-A reflects a role of this protein in mRNA translational regulation. In support of this hypothesized role, we demonstrate that VCX-A can specifically bind a subset of mRNAs involved in neuritogenesis and is also capable of promoting translational silencing. Thus, VCX-A contains the capacity to modulate the stability and translation of a subset of target mRNAs involved in neuronal differentiation and arborization. It is plausible that defects of these functions in the absence of the VCX genes could contribute to a mental retardation phenotype.
Authors:
Xinfu Jiao; Hongxin Chen; Jianmin Chen; Karl Herrup; Bonnie L Firestein; Megerditch Kiledjian
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  29     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-08     Completed Date:  2009-11-10     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12419-27     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Patterning
Cell Differentiation
Cell Line
Cells, Cultured
Gene Expression Regulation
Gene Silencing
Humans
Mental Retardation, X-Linked / genetics*
Mice
Neurites / physiology*
Neurons / cytology,  metabolism
Nuclear Proteins / metabolism*
Protein Biosynthesis / physiology
RNA / metabolism
Grant Support
ID/Acronym/Agency:
AG024494/AG/NIA NIH HHS; GM67005/GM/NIGMS NIH HHS; NS20591/NS/NINDS NIH HHS; R01 GM067005/GM/NIGMS NIH HHS; R01 GM067005-05A1/GM/NIGMS NIH HHS; R01 NS020591/NS/NINDS NIH HHS; R01 NS020591-27/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/VCX protein, human; 63231-63-0/RNA
Comments/Corrections

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