Fragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
TLDR
New studies suggest a possible local function of FMRP in axons that may be important for guidance, synaptic development, and formation of neural circuits.About:
This article is published in Neuron.The article was published on 2008-10-23 and is currently open access. It has received 992 citations till now. The article focuses on the topics: MRNA transport & Fragile X syndrome.read more
Citations
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Journal ArticleDOI
FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism
Jennifer C. Darnell,Sarah J. Van Driesche,Chaolin Zhang,Ka Ying Sharon Hung,Aldo Mele,Claire E. Fraser,Elizabeth F. Stone,Cynthia Chen,John J. Fak,Sung Wook Chi,Donny D. Licatalosi,Joel D. Richter,Robert B. Darnell,Robert B. Darnell +13 more
TL;DR: A brain polyribosome-programmed translation system is developed, revealing that FMRP reversibly stalls ribosomes specifically on its target mRNAs and suggests multiple targets for clinical intervention in FXS and ASD.
Journal ArticleDOI
Behavioural phenotyping assays for mouse models of autism
TL;DR: Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
Journal ArticleDOI
mRNA Localization: Gene Expression in the Spatial Dimension
Kelsey C. Martin,Anne Ephrussi +1 more
TL;DR: This Review focuses on cis-acting RNA localization elements, RNA-binding proteins, and the assembly of mRNAs into granules that are transported by molecular motors along cytoskeletal elements to their final destination in the cell.
Journal ArticleDOI
Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
Dieter Edbauer,Joel R. Neilson,Kelly A. Foster,Chi-Fong Wang,Daniel P. Seeburg,Matthew N. Batterton,Tomoko Tada,Bridget M. Dolan,Phillip A. Sharp,Morgan Sheng +9 more
TL;DR: In this article, the NMDA receptor subunit NR2A was identified as a target of miR-125b and showed that NR 2A mRNA is specifically associated with FMRP in brain.
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Advancing the understanding of autism disease mechanisms through genetics
TL;DR: Current understanding of the genetic architecture of ASD is reviewed and genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology are integrated.
References
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Journal ArticleDOI
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Annemiske J.M.H. Verkerk,Maura Pieretti,James S. Sutcliffe,Ying-Hui Fu,Derek P.A. Kuhl,Antonio Pizzuti,Orly Reiner,Stephen Richards,Maureen F. Victoria,Fuping Zhang,Bert Eussen,Gert-Jan B. van Ommen,Lau Blonden,Gregory J. Riggins,Jane L. Chastain,Catherine B. Kunst,Hans Galjaard,C. Thomas Caskey,David L. Nelson,Ben A. Oostra,Stephen T. Warren +20 more
TL;DR: A fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes is identified and localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.
Journal ArticleDOI
Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox.
Ying-Hui Fu,Derek P.A. Kuhl,Antonio Pizzuti,Maura Pieretti,James S. Sutcliffe,James S. Sutcliffe,Stephen Richards,Annemieke J.M.H. Verkert,Jeanette J. A. Holden,Raymond G. Fenwick,Stephen T. Warren,Stephen T. Warren,Ben A. Oostra,David L. Nelson,C. Thomas Caskey +14 more
TL;DR: The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.
Journal ArticleDOI
A brain-specific microRNA regulates dendritic spine development
Gerhard Schratt,Fabian Tuebing,Elizabeth A. Nigh,Elizabeth A. Nigh,Christina G. Kane,Christina G. Kane,Mary E. Sabatini,Michael A. Kiebler,Michael E. Greenberg,Michael E. Greenberg +9 more
TL;DR: It is shown that a brain-specific microRNA, miR-134>, is localized to the synapto-dendritic compartment of rat hippocampal neurons and negatively regulates the size of dendritic spines—postsynaptic sites of excitatory synaptic transmission.
Journal ArticleDOI
The mGluR theory of fragile X mental retardation
TL;DR: Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus, consistent with the growing evidence that FMRP normally functions as a repressor of translation of specific mRNAs.
Journal ArticleDOI
Altered synaptic plasticity in a mouse model of fragile X mental retardation
TL;DR: It is shown that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP.
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The mGluR theory of fragile X mental retardation
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Annemiske J.M.H. Verkerk,Maura Pieretti,James S. Sutcliffe,Ying-Hui Fu,Derek P.A. Kuhl,Antonio Pizzuti,Orly Reiner,Stephen Richards,Maureen F. Victoria,Fuping Zhang,Bert Eussen,Gert-Jan B. van Ommen,Lau Blonden,Gregory J. Riggins,Jane L. Chastain,Catherine B. Kunst,Hans Galjaard,C. Thomas Caskey,David L. Nelson,Ben A. Oostra,Stephen T. Warren +20 more