scholarly journals Hypothesis: A Role for Fragile X Mental Retardation Protein in Mediating and Relieving MicroRNA-Guided Translational Repression?

2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Isabelle Plante ◽  
Patrick Provost
Keyword(s):  
Mental Retardation ◽  
Messenger Rna ◽  
Mammalian Cells ◽  
Fragile X ◽  
Strand Exchange ◽  
Translational Repression ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Cellular Signal ◽  
Reverse Strand

MicroRNA (miRNA)-guided messenger RNA (mRNA) translational repression is believed to be mediated by effector miRNA-containing ribonucleoprotein (miRNP) complexes harboring fragile X mental retardation protein (FMRP). Recent studies documented the nucleic acid chaperone properties of FMRP and characterized its role and importance in RNA silencing in mammalian cells. We propose a model in which FMRP could facilitate miRNA assembly on target mRNAs in a process involving recognition of G quartet structures. Functioning within a duplex miRNP, FMRP may also mediate mRNA targeting through a strand exchange mechanism, in which the miRNA*of the duplex is swapped for the mRNA. Furthermore, FMRP may contribute to the relief of miRNA-guided mRNA repression through a reverse strand exchange reaction, possibly initiated by a specific cellular signal, that would liberate the mRNA for translation. Suboptimal utilization of miRNAs may thus account for some of themolecular defects in patients with the fragile X syndrome.

scholarly journals Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P

1999 ◽  
Vol 343 (3) ◽  
pp. 517-523 ◽  
Author(s):  
Filippo TAMANINI ◽  
Leontine VAN UNEN ◽  
Cathy BAKKER ◽  
Nicoletta SACCHI ◽  
Hans GALJAARD ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Mammalian Cells ◽  
Fragile X ◽  
Gel Filtration ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Heterotypic Interactions ◽  
Molecular Masses ◽  
Related Proteins

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a role in RNA metabolism. To characterize a possible functional role of the interacting proteins the complex formation of the FXR proteins was studied in mammalian cells. Double immunofluorescence analysis in COS cells over-expressing either FMRP ISO12/FXR1P or FMRP ISO12/FXR2P confirmed heterotypic interactions. However, Western-blotting studies on cellular homogenates containing physiological amounts of the three proteins gave different indications. Gel-filtration experiments under physiological as well as EDTA conditions showed that the FXR proteins were in complexes of > 600 kDa, as parts of messenger ribonuclear protein (mRNP) particles associated with polyribosomes. Salt treatment shifted FMRP, FXR1P and FXR2P into distinct intermediate complexes, with molecular masses between 200 and 300 kDa. Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes. Further analysis by [35S]methionine labelling in vivo followed by immunoprecipitation indicated that no proteins other than the FXR proteins were present in these complexes. These results suggest that the FXR proteins form homo-multimers preferentially under physiological conditions in mammalian cells, and might participate in mRNP particles with separate functions.

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

2006 ◽  
Vol 2006 ◽  
pp. 1-12 ◽  
Author(s):  
Isabelle Plante ◽  
Laetitia Davidovic ◽  
Dominique L. Ouellet ◽  
Lise-Andrée Gobeil ◽  
Sandra Tremblay ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Translational Control ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Fragile X ◽  
Rna Sequences ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Rnp Complex

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.

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