title: Modulation of neuritogenesis by a protein implicated in X-linked mental retardation.
abstract: 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.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854-8082, USA.
authors.forename: Xinfu
authors.initials: X
authors.lastname: Jiao
authors.forename: Hongxin
authors.initials: H
authors.lastname: Chen
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.forename: Karl
authors.initials: K
authors.lastname: Herrup
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Firestein
authors.forename: Megerditch
authors.initials: M
authors.lastname: Kiledjian
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051379:Mice; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology; D012313:RNA / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C404411:VCX protein, human; D012313:RNA