The translation of translational control by FMRP

Therapeutic targets for FXS

Jennifer C. Darnell, Eric Klann

Research output: Contribution to journalArticle

Abstract

De novo protein synthesis is necessary for long-lasting modifications in synaptic strength and dendritic spine dynamics that underlie cognition. Fragile X syndrome (FXS), characterized by intellectual disability and autistic behaviors, holds promise for revealing the molecular basis for these long-term changes in neuronal function. Loss of function of the fragile X mental retardation protein (FMRP) results in defects in synaptic plasticity and cognition in many models of the disease. FMRP is a polyribosome-associated RNA-binding protein that regulates the synthesis of a set of plasticity-reated proteins by stalling ribosomal translocation on target mRNAs. The recent identification of mRNA targets of FMRP and its upstream regulators, and the use of small molecules to stall ribosomes in the absence of FMRP, have the potential to be translated into new therapeutic avenues for the treatment of FXS.

Original languageEnglish (US)
Pages (from-to)1530-1536
Number of pages7
JournalNature Neuroscience
Volume16
Issue number11
DOIs
StatePublished - Nov 2013

Fingerprint

Fragile X Mental Retardation Protein
Fragile X Syndrome
Cognition
Dendritic Spines
Messenger RNA
Neuronal Plasticity
RNA-Binding Proteins
Polyribosomes
Ribosomal Proteins
Therapeutics
Ribosomes
Intellectual Disability
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The translation of translational control by FMRP : Therapeutic targets for FXS. / Darnell, Jennifer C.; Klann, Eric.

In: Nature Neuroscience, Vol. 16, No. 11, 11.2013, p. 1530-1536.

Research output: Contribution to journalArticle

@article{830812b3f21043a68b32097c41a257c2,
title = "The translation of translational control by FMRP: Therapeutic targets for FXS",
abstract = "De novo protein synthesis is necessary for long-lasting modifications in synaptic strength and dendritic spine dynamics that underlie cognition. Fragile X syndrome (FXS), characterized by intellectual disability and autistic behaviors, holds promise for revealing the molecular basis for these long-term changes in neuronal function. Loss of function of the fragile X mental retardation protein (FMRP) results in defects in synaptic plasticity and cognition in many models of the disease. FMRP is a polyribosome-associated RNA-binding protein that regulates the synthesis of a set of plasticity-reated proteins by stalling ribosomal translocation on target mRNAs. The recent identification of mRNA targets of FMRP and its upstream regulators, and the use of small molecules to stall ribosomes in the absence of FMRP, have the potential to be translated into new therapeutic avenues for the treatment of FXS.",
author = "Darnell, {Jennifer C.} and Eric Klann",
year = "2013",
month = "11",
doi = "10.1038/nn.3379",
language = "English (US)",
volume = "16",
pages = "1530--1536",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - The translation of translational control by FMRP

T2 - Therapeutic targets for FXS

AU - Darnell, Jennifer C.

AU - Klann, Eric

PY - 2013/11

Y1 - 2013/11

N2 - De novo protein synthesis is necessary for long-lasting modifications in synaptic strength and dendritic spine dynamics that underlie cognition. Fragile X syndrome (FXS), characterized by intellectual disability and autistic behaviors, holds promise for revealing the molecular basis for these long-term changes in neuronal function. Loss of function of the fragile X mental retardation protein (FMRP) results in defects in synaptic plasticity and cognition in many models of the disease. FMRP is a polyribosome-associated RNA-binding protein that regulates the synthesis of a set of plasticity-reated proteins by stalling ribosomal translocation on target mRNAs. The recent identification of mRNA targets of FMRP and its upstream regulators, and the use of small molecules to stall ribosomes in the absence of FMRP, have the potential to be translated into new therapeutic avenues for the treatment of FXS.

AB - De novo protein synthesis is necessary for long-lasting modifications in synaptic strength and dendritic spine dynamics that underlie cognition. Fragile X syndrome (FXS), characterized by intellectual disability and autistic behaviors, holds promise for revealing the molecular basis for these long-term changes in neuronal function. Loss of function of the fragile X mental retardation protein (FMRP) results in defects in synaptic plasticity and cognition in many models of the disease. FMRP is a polyribosome-associated RNA-binding protein that regulates the synthesis of a set of plasticity-reated proteins by stalling ribosomal translocation on target mRNAs. The recent identification of mRNA targets of FMRP and its upstream regulators, and the use of small molecules to stall ribosomes in the absence of FMRP, have the potential to be translated into new therapeutic avenues for the treatment of FXS.

UR - http://www.scopus.com/inward/record.url?scp=84886953546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886953546&partnerID=8YFLogxK

U2 - 10.1038/nn.3379

DO - 10.1038/nn.3379

M3 - Article

VL - 16

SP - 1530

EP - 1536

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 11

ER -