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
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Loss of fragile X protein FMRP impairs homeostatic synaptic downscaling through tumor suppressor p53 and ubiquitin E3 ligase Nedd4-2.
TL;DR: A novel cellular mechanism underlying synaptic downscaling is discovered, the dysregulation and successful restoration of this mechanism are demonstrated in the FXS mouse model, and a pharmacological inhibitor of p53, Nedd4-2 phosphorylation, GluA1 ubiquitination and synapticDownscaling are all restored in Fmr1 KO neurons.
Journal ArticleDOI
Synaptic control of local translation: the plot thickens with new characters
Maria Gabriela Thomas,Maria Gabriela Thomas,Malena Lucía Pascual,Malena Lucía Pascual,Malena Lucía Pascual,Dario Maschi,Dario Maschi,Luciana Luchelli,Luciana Luchelli,Graciela Lidia Boccaccio,Graciela Lidia Boccaccio,Graciela Lidia Boccaccio +11 more
TL;DR: Current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics is summarized.
Journal ArticleDOI
Dysregulation of mTOR signaling in neuropsychiatric disorders: therapeutic implications.
Kirsty Sawicka,R. Suzanne Zukin +1 more
TL;DR: The mTOR pathway is a central regulator of cell growth, proliferation, survival, and cap-dependent protein translation and growing evidence indicates that dysregulation of mTOR is involved in human diseases, including cancer, diabetes, and autism.
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Fmrp targets or not: long, highly brain-expressed genes tend to be implicated in autism and brain disorders.
TL;DR: It is suggested that the overlap between Fmrp targets and neuropsychiatric candidate genes might be secondary to simple features such as transcript length and robust expression in the brain, and comparison of known FMRp-binding targets to candidate gene lists should be informed by both of these features.
Journal ArticleDOI
Dysregulated Translation in Neurodevelopmental Disorders: An Overview of Autism-Risk Genes Involved in Translation
TL;DR: The autism‐risk gene list is taken and the molecules that (perhaps) are involved in mRNA transport and translation are discussed, including some proof‐of‐principle regimens for use in autism mouse models to correct dysregulated translation.
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