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
More filters
Journal ArticleDOI
Selective inhibition of glycogen synthase kinase 3α corrects pathophysiology in a mouse model of fragile X syndrome
Patrick K. McCamphill,Laura J. Stoppel,Rebecca K Senter,Michael C. Lewis,Arnold J. Heynen,David C. Stoppel,Vinay Sridhar,Katie A. Collins,Xi Shi,Jen Q. Pan,Jon M. Madison,Jeffrey R. Cottrell,Kimberly M. Huber,Edward M. Scolnick,Edward B. Holson,Florence F. Wagner,Mark F. Bear +16 more
TL;DR: It is shown that inhibition of GSK3α, but not G SK3β, corrected aberrant protein synthesis, audiogenic seizures, and sensory cortex hyperexcitability in Fmr1−/y mice, and GSK2α selective inhibitors may have potential as a therapeutic approach for treating fragile X syndrome.
Journal ArticleDOI
Defects in translational regulation contributing to human cognitive and behavioral disease.
TL;DR: New approaches to the unbiased in vivo identification of maps of binding sites for these proteins on mRNA is expected to greatly increase understanding of this crucial level of regulation in neuronal development and function.
Posted ContentDOI
Tunable protein synthesis by transcript isoforms in human cells
TL;DR: The results expose the large dynamic range of transcript-isoform- specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels.
Journal ArticleDOI
Nuclear Fragile X Mental Retardation Protein Is localized to Cajal Bodies
Alain Y. Dury,Rachid El Fatimy,Sandra Tremblay,Timothy M. Rose,Jocelyn Côté,Paul De Koninck,Edouard W. Khandjian +6 more
TL;DR: It is shown here that the most commonly expressed human FMRP isoforms (ISO1 and 7) do not localize to the nucleus, and a missense mutation (I304N), known to alter the KH2-mediated RNA binding properties of FMRp, abolishes the localization of human F MRP ISO6 to Cajal bodies.
Journal ArticleDOI
Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D).
Mark E. Gurney,Patricia Cogram,Patricia Cogram,Robert M. J. Deacon,Robert M. J. Deacon,Christopher S. Rex,Michael Tranfaglia +6 more
TL;DR: Daily treatment of adult male fmr1 C57Bl6 knock-out mice with BPN14770 for 14 days reduced hyperarousal, improved social interaction, and improved natural behaviors such as nesting and marble burying as well as dendritic spine morphology, indicating that the drug may be useful for the treatment of fragile-X syndrome and other disorders with decreased cAMP signaling.
References
More filters
Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Biometery: The principles and practice of statistics in biological research
TL;DR: In this paper, the authors present a model for the analysis of variance in a single-classification and two-way and multiway analysis of Variance with the assumption of correlation.
Book
Biometry: The Principles and Practice of Statistics in Biological Research
Robert R. Sokal,F. James Rohlf +1 more
TL;DR: In this paper, the authors present a model for the analysis of variance in a single-classification and two-way and multiway analysis of Variance with the assumption of correlation.
Journal ArticleDOI
Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
TL;DR: The hierarchical model of Lonnstedt and Speed (2002) is developed into a practical approach for general microarray experiments with arbitrary numbers of treatments and RNA samples and the moderated t-statistic is shown to follow a t-distribution with augmented degrees of freedom.
Related Papers (5)
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