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