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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High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells
TL;DR: The data provide proof of principle that this assay combined with FXS patient‐derived neural stem cells can be used in a high‐throughput format to identify better lead compounds for FXS drug development.
Journal ArticleDOI
GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome.
D Sinclair,Robert E. Featherstone,M. Naschek,J. Nam,A. Du,Suzie Wright,K. Pance,O. Melnychenko,Rachel Weger,Shinobu Akuzawa,Mitsuyuki Matsumoto,Steven J. Siegel +11 more
TL;DR: It is suggested that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome, a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity.
Journal ArticleDOI
Rapid Molecular Profiling of Defined Cell Types Using Viral TRAP
Alexander R. Nectow,Alexander R. Nectow,Maria V. Moya,Mats I. Ekstrand,Awni Mousa,Kelly L. McGuire,Caroline E. Sferrazza,Bianca C. Field,Gabrielle S. Rabinowitz,Kirsty Sawicka,Yupu Liang,Jeffrey M. Friedman,Nathaniel Heintz,Eric F. Schmidt +13 more
TL;DR: A versatile strategy for profiling CNS cell types in a spatiotemporally restricted fashion by engineering a Cre-dependent adeno-associated virus expressing an EGFP- tagged ribosomal protein to access translating mRNAs by translating ribosome affinity purification (TRAP).
Journal ArticleDOI
BDNF Stimulation of Protein Synthesis in Cortical Neurons Requires the MAP Kinase-Interacting Kinase MNK1
Maja Genheden,Justin W. Kenney,Harvey E. Johnston,Antigoni Manousopoulou,Antigoni Manousopoulou,Spiros D. Garbis,Spiros D. Garbis,Christopher G. Proud +7 more
TL;DR: Using a combination of pharmacological and genetic approaches, it is shown that BDNF-induced upregulation of protein synthesis requires MEK/ERK signaling and the downstream kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E.
Journal ArticleDOI
Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome.
Bin Tang,Tingting Wang,Huida Wan,Li Han,Xiaoyan Qin,Yaoyang Zhang,Jian Wang,Chunlei Yu,Fulvia Berton,Walter Francesconi,John R. Yates,Peter W. Vanderklish,Lujian Liao +12 more
TL;DR: This study used quantitative mass spectrometry to systematically compare protein expression in neocortical synaptic fractions between Fmr1 (fragile X mental retardation 1) knockout (KO) and wild-type mice during adolescence and adulthood and discovered an upregulation of a large number of synaptic proteins in young KO mice but not in adult ones.
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.
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