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, Hervé Moine

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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 after translation arrest.

Original languageEnglish
Pages (from-to)428-437
Number of pages10
JournalMolecular Biology of the Cell
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Jan 2009
Externally publishedYes

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Fragile X Mental Retardation Protein
RNA Interference
Messenger RNA
Neuronal Plasticity
RNA-Binding Proteins
Protein Biosynthesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cells lacking the fragile X mental retardation protein (FMRP) have normal RISC activity but exhibit altered stress granule assembly. / Didiot, Marie Cécile; Subramanian, Murugan; Flatter, Eric; Mandel, Jean Louis; Moine, Hervé.

In: Molecular Biology of the Cell, Vol. 20, No. 1, 01.01.2009, p. 428-437.

Research output: Contribution to journalArticle

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