News & Views | Published:

A new regulatory pathway for fragile X syndrome?


One out of every 4,500 males suffers cognitive impairment due to alterations in the fragile X gene. The gene has a complicated biology, and it may have just gotten a bit more complex. The fragile X gene product in flies could play a role in regulation by small RNA molecules.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    O'Donnell, W.T. & Warren, S.T. A decade of molecular studies of fragile X syndrome. Annu. Rev. Neurosci. 25, 315–338 (2002).

  2. 2

    Tassone, F. et al. Elevated levels of FMR1 mRNA in carrier males: A new mechanism of involvement in the fragile-X syndrome. Am. J. Hum. Genet. 66, 6–15 (2000).

  3. 3

    Greco, C.M. et al. Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125, 1760–1771 (2002).

  4. 4

    Ishizuka, A., Siomi, M.C. & Siomi, H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev. 16, 2497–2508 (2002).

  5. 5

    Caudy, A.A., Myers, M., Hannon, G.J. & Hammond, S.M. Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev. 16, 2491–2496 (2002).

  6. 6

    McManus, M.T. & Sharp, P.A. Gene silencing in mammals by small interfering RNAs. Nature Rev. Genet. 3, 737–47 (2002).

  7. 7

    Hutvagner, G. & Zamore, P.D. RNAi: Nature abhors a double-strand. Curr. Opin. Genet. Dev. 12, 225–232 (2002).

  8. 8

    Allshire, R. RNAi and heterochromatin—a hushed-up affair. Science 297, 1818–1819 (2002).

  9. 9

    Hutvagner, G. & Zamore, P.D. A microRNA in a multiple-turnover RNAi enzyme complex. Science 297, 2056–2060 (2002).

  10. 10

    Mourelatos, Z. et al. miRNPs: A novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 16, 720–728 (2002).

  11. 11

    Heaton, J.H., Dlakic, W.M., Dlakic, M. & Gelehrter, T.D. Identification and cDNA cloning of a novel RNA-binding protein that interacts with the cyclic nucleotide-responsive sequence in the Type-1 plasminogen activator inhibitor mRNA. J. Biol. Chem. 276, 3341–3347 (2001).

  12. 12

    Laggerbauer, B., Ostareck, D., Keidel, E.M., Ostareck-Lederer, A. & Fischer, U. Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum. Mol. Genet. 10, 329–338 (2001).

  13. 13

    Hansen, R.S., Canfield, T.K., Lamb, M.M., Gartler, S.M. & Laird, C.D. Association of fragile X syndrome with delayed replication of the FMR1 gene. Cell 73, 1403–1409 (1993).

  14. 14

    Stöger, R., Kajimura, T.M., Brown, W.T. & Laird, C.D. Epigenetic variation illustrated by DNA methylation patterns of the fragile-X gene FMR1. Hum. Mol. Genet. 6, 1791–1801 (1997).

  15. 15

    Hagerman, R.J. et al. Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 57, 127–130 (2001).

  16. 16

    Weiler, I.J. et al. Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc. Natl. Acad. Sci. USA 94, 5395–5400 (1997).

Download references

Author information

Rights and permissions

To obtain permission to re-use content from this article visit RightsLink.

About this article

Figure 1: Some adult males with premutation alleles of the fragile X syndrome have presented with a late-onset, neurological syndrome not evident in patients with classic fragile X syndrome.

a, courtesy of C. Greco and P. Hagerman; b, reprinted with permission from Brain.