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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A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome.
TL;DR: ASD symptoms increased in FXS with age, and social language impairment emerged as a potential core shared feature of FXS and ASD that may help elucidate underlying molecular genetic variation related to phenotypic variance, and aid intervention planning for subgroups of children showing distinct phenotypes.
Journal ArticleDOI
Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice.
TL;DR: RSK is identified as a therapeutic target for fragile X and the therapeutic potential of drugs for the treatment of FXS may vary in a brain-region–specific manner, as evidenced by the site of elevated phosphorylation and the finding that ERK inhibition corrects elevated RSK and S6 activity.
Journal ArticleDOI
Toward a Genome-Wide Landscape of Translational Control
TL;DR: Genome-wide studies that use high-throughput techniques and bioinformatics to assess the role of mRNA translation in the regulation of protein levels are reviewed and how genome-wide data on mRNA translation can be obtained, analyzed, and used to identify mechanisms of translational control are discussed.
Journal ArticleDOI
Digital expression profiling of the compartmentalized translatome of Purkinje neurons
Anton Kratz,Pascal Beguin,Megumi Kaneko,Takahiko Chimura,Ana Maria Suzuki,Atsuko Matsunaga,Sachi Kato,Nicolas Bertin,Timo Lassmann,Réjan Vigot,Piero Carninci,Charles Plessy,Thomas Launey +12 more
TL;DR: This work combined microdissection, translating ribosome affinity purification in nontransgenic animals, and quantitative nanoCAGE sequencing to obtain a snapshot of RNAs bound to cytoplasmic or rough endoplasmic reticulum (rER)-associated ribosomes in the PC and its dendrites, which allowed it to discover novel markers of PCs.
Journal ArticleDOI
Protein synthesis levels are increased in a subset of individuals with fragile X syndrome.
Sébastien Jacquemont,Laura Pacini,Aia E. Jønch,Giulia Cencelli,Izabela Rozenberg,Yunsheng He,Laura D'Andrea,Giorgia Pedini,Marwa Eldeeb,Rob Willemsen,Fabrizio Gasparini,Flora Tassone,Randi J Hagerman,Baltazar Gomez-Mancilla,Baltazar Gomez-Mancilla,Claudia Bagni,Claudia Bagni +16 more
TL;DR: It is suggested that a significant proportion, but not all individuals with FXS, may benefit from the reduction of excessive levels of protein synthesis, and a potential explanation for the comprehensive drug development program undertaken thus far yielding negative results.
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