Cells lacking the fragile X mental retardation protein (FMRP) have normal RISC activity but exhibit altered stress granule assembly.

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.
Type de document :
Article dans une revue
Molecular Biology of the Cell, American Society for Cell Biology, 2009, 20 (1), pp.428-37. 〈10.1091/mbc.E08-07-0737〉
Liste complète des métadonnées

Littérature citée [47 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00357408
Contributeur : Maité Peney <>
Soumis le : mardi 26 octobre 2010 - 17:35:27
Dernière modification le : jeudi 11 janvier 2018 - 06:17:43
Document(s) archivé(s) le : jeudi 27 janvier 2011 - 02:27:17

Fichier

428.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Marie-Cécile Didiot, Murugan Subramanian, Eric Flatter, Jean-Louis Mandel, Hervé Moine. Cells lacking the fragile X mental retardation protein (FMRP) have normal RISC activity but exhibit altered stress granule assembly.. Molecular Biology of the Cell, American Society for Cell Biology, 2009, 20 (1), pp.428-37. 〈10.1091/mbc.E08-07-0737〉. 〈inserm-00357408〉

Partager

Métriques

Consultations de la notice

189

Téléchargements de fichiers

355