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First in vivo evidence of microRNA-induced fragile X mental retardation syndrome

Molecular Psychiatry volume 11, pages 616–617 (2006)Cite this article

Fragile X syndrome (FraX) is the most common form of inherited mental retardation, with the estimated prevalence of 30% of total human mental retardation disorders, and is also among the most frequent single gene disorders.1 The gene affected by the syndrome in 99% patients, FMR1, is transcriptionally inactivated by the expansion and the methylation of trinucleotide (CGG) repeats, located in the 5′-untranslated region (5′-UTR) of the gene.2 FMR1 encodes an RNA-binding protein, FMRP, which is associated with polyribosome assembly in an RNA-dependent manner and capable of suppressing protein translation through an RNA interference (RNAi)-like pathway that is important for neuronal development and plasticity. However, no appropriate animal model is available for the study of FraX etiology because current Drosophila and mouse models are all based on the gene deletion of FMRP, completely irrelevant to the mechanism of RNAi.

Many recent studies have indicated that human FraX results from microRNA (miRNA)-mediated methylation in the CpG region of FMR1 rCGG expansion, which is targeted by a small RNA derived from the 3′-UTR of the FMR1 expanded allele transcript.3, 4, 5 Such dicer-processed miRNA may trigger the formation of RNA-induced initiator of transcriptional gene silencing (RITS) on the homologous r(CGG) repeats and leads to heterochromatin repression of the FMR1 locus. Thus, the etiological mechanism of FraX is owing to the miRNA-mediated genomic suppression in FMR1, rather than gene deletion.

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References

  1. Hagerman RJ, Staley LW, O'Conner R, Lugenbeel K, Nelson D, McLean SD et al. Pediatrics 1996; 97: 122–126.

  2. Imbert G, Kretz C, Johnson K, Mandel JL . Nat Genet 1993; 4: 72–76.

  3. Ishizuka A, Siomi MC, Siomi H . Genes Dev 2002; 16: 2497–2508.

  4. Caudy AA, Myers M, Hannon GJ, Hammond SM . Genes Dev 2002; 16: 2491–2496.

  5. Jin P, Alisch RS, Warren ST . Nat Cell Biol 2004; 6: 1048–1053.

  6. Tucker B, Richards R, Lardelli M . Dev Genes Evol 2004; 214: 567–574.

  7. Lin SL, Chang D, Ying SY . Gene 2005; 356: 32–38.

  8. Huber KM, Gallagher SM, Warren ST, Bear MF . Proc Natl Acad Sci USA 2002; 99: 7746–7750.

  9. Irwin SA, Christmon CA, Grossman AW, Galvez R, Kim SH, DeGrush BJ et al. Neurobiol Learn Mem 2005; 83: 180–187.

  10. Galvez R, Gopal AR, Greenough WT . Brain Res 2003; 971: 83–89.

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  1. Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    S-L Lin, S-Je Chang & S-Y Ying

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  1. S-L Lin
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Correspondence to S-L Lin.

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Lin, SL., Chang, SJ. & Ying, SY. First in vivo evidence of microRNA-induced fragile X mental retardation syndrome. Mol Psychiatry 11, 616–617 (2006). https://doi.org/10.1038/sj.mp.4001828

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