Journal of Biomedicine and Biotechnology 
Volume 2006 (2006), Article ID 64347, 12 pages
doi:10.1155/JBB/2006/64347
Research Article

Dicer-Derived MicroRNAs Are Utilized by the Fragile X Mental Retardation Protein for Assembly on Target RNAs

Isabelle Plante,1,2 Laetitia Davidovic,2,3 Dominique L. Ouellet,1,2 Lise-Andrée Gobeil,1,2 Sandra Tremblay,2,3 Edouard W. Khandjian,2,3 and Patrick Provost1,2

 1Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUL-CHUQ, 2705 Blvd. Laurier, Sainte-Foy G1V 4G2, QC, Canada
2Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Quebec G1K 7P4, QC, Canada
3Unité de Recherche en Génétique Humaine et Moléculaire, Centre de Recherche Hôpital St-Francois d'Assise-CHUQ, G1L 3L5, QC, Canada
Received 27 April 2006; Accepted 30 May 2006

Abstract

In mammalian cells, fragile X mental retardation protein (FMRP) has been reported to be part of a microRNA (miRNA)-containing effector ribonucleoprotien (RNP) complex believed to mediate translational control of specific mRNAs. Here, using recombinant proteins, we demonstrate that human FMRP can act as a miRNA acceptor protein for the ribonuclease Dicer and facilitate the assembly of miRNAs on specific target RNA sequences. The miRNA assembler property of FMRP was abrogated upon deletion of its single-stranded (ss) RNA binding K-homology domains. The requirement of FMRP for efficient RNA interference (RNAi) in vivo was unveiled by reporter gene silencing assays using various small RNA inducers, which also supports its involvement in an ss small interfering RNA (siRNA)-containing RNP (siRNP) effector complex in mammalian cells. Our results define a possible role for FMRP in RNA silencing and may provide further insight into the molecular defects in patients with the fragile X syndrome.