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

[摘要] In mammalian cells, fragile X mental retardation protein (FMRP)has been reported to be part of a microRNA (miRNA)-containingeffector ribonucleoprotien (RNP) complex believed to mediatetranslational control of specific mRNAs. Here, using recombinantproteins, we demonstrate that human FMRP can act as a miRNAacceptor protein for the ribonuclease Dicer and facilitate theassembly of miRNAs on specific target RNA sequences. The miRNAassembler property of FMRP was abrogated upon deletion of itssingle-stranded (ss) RNA binding K-homology domains. Therequirement of FMRP for efficient RNA interference (RNAi) in vivowas unveiled by reporter gene silencing assays using various smallRNA inducers, which also supports its involvement in an ss smallinterfering RNA (siRNA)-containing RNP (siRNP) effector complex inmammalian cells. Our results define a possible role for FMRP inRNA silencing and may provide further insight into the moleculardefects in patients with the fragile X syndrome.

[学科分类] 基础医学