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MBC in Press, published online ahead of print November 12, 2008
Mol. Biol. Cell 10.1091/mbc.E08-07-0737

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Submitted on July 18, 2008
Revised on October 22, 2008
Accepted on October 30, 2008

Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly

Marie-Cécile Didiot, Murugan Subramanian, Eric Flatter, Jean-Louis Mandel, and Hervé Moine

IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire); Inserm, U596; CNRS, UMR7104; Université Louis Pasteur; Collège de France, Chaire de Génétique Humaine, 1 rue Laurent Fries, Illkirch-Graffenstaden, F-67404 France

Monitoring Editor: A. Gregory Matera

The fragile X mental retardation protein (FMRP) is an RNA binding protein involved in the mRNA metabolism. The absence of FMRP in neurons leads to alterations of the synaptic plasticity, probably as a result of translation regulation defects. The exact molecular mechanisms by which FMRP plays a role in translation regulation have remained elusive. The finding of an interaction between FMRP and the RNA Interference Silencing Complex (RISC), a master of translation regulation, has suggested that both regulators could be functionally linked. We investigated here this link and we show that FMRP exhibits little overlap both physically and functionally with the RISC machinery, excluding a direct impact of FMRP on RISC function. Our data indicate that FMRP and RISC are associated to distinct pools of mRNAs. FMRP, unlike RISC machinery, associates with the pool of mRNAs that eventually goes into stress granules upon cellular stress. Furthermore, we show that FMRP plays a positive role in this process as the lack of FMRP or a point mutant causing a severe fragile X alter stress granule formation. Our data support the proposal that FMRP plays a role in controlling the fate of mRNAs following translation arrest.


Address correspondence to: Hervé Moine (moine{at}igbmc.u-strasbg.fr)







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