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
TLDR
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.About:
This article is published in Cell.The article was published on 2011-07-22 and is currently open access. It has received 1861 citations till now. The article focuses on the topics: FMR1 & RNA-binding protein.read more
Citations
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Reduced Phenotypic Severity Following Adeno-Associated Virus-Mediated Fmr1 Gene Delivery in Fragile X Mice
TL;DR: These results provide the first proof of principle that gene therapy can correct specific behavioral abnormalities in the mouse model of FXS and reverse phenotypic deficits in the Fmr1 knockout mouse model.
Journal ArticleDOI
FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory.
Kirsty Sawicka,Caryn R Hale,Christopher Y. Park,John J. Fak,Jodi Gresack,Sarah J. Van Driesche,Jin Joo Kang,Jennifer C. Darnell,Robert B. Darnell,Robert B. Darnell +9 more
TL;DR: Differences in FMRP-dependent regulation of mRNAs across neuronal cell types that may contribute to phenotypes such as memory defects and sleep disturbance associated with FXS are demonstrated.
Journal ArticleDOI
The MAP kinase-interacting kinases regulate cell migration, vimentin expression and eIF4E/CYFIP1 binding.
James E. Beggs,Shuye Tian,Greg G. Jones,Jianling Xie,Valentina Iadevaia,Veronika Jenei,Gareth J. Thomas,Christopher G. Proud +7 more
TL;DR: Inhibition or genetic knockout of the Mnks increased the binding of eIF4E to the cytoplasmic FMRP-interacting protein 1 (CYFIP1), which binds the fragile-X mental retardation protein, F MRP, a translational repressor, potentially providing a molecular mechanism for the control of cell migration by the Mnk.
Journal ArticleDOI
Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome
TL;DR: Evidence is provided that the functional expression of h-channels (Ih) is down-regulated, whereas A-type K+ channel function is up-regulated in pyramidal tract-projecting neurons in the fmr1-/y mouse PFC, suggesting cell-type-specific phenotypes for the disease.
Journal ArticleDOI
The Roles of FMRP-Regulated Genes in Autism Spectrum Disorder: Single- and Multiple-Hit Genetic Etiologies
TL;DR: The Trend test is developed, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches and is easily extendible to combining information from multiple types of genetic variation, increasing its value to next-generation sequencing approaches.
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