Twin-track approach to fragile x

Access through your institution Buy or subscribe The study by Victoria Brown, Peng Jin and colleagues involved two microarray experiments. In the first, mRNA isolated from mouse brain was

compared with mRNA that had been immunoprecipitated with an FMR1 antibody, the aim being to find mRNA that was bound to FMR1. Of the >25,000 genes screened, 432 were identified that were

enriched by immunoprecipitation. The second study compared polysomal RNA from fragile X with control human cell lines. The authors reasoned that if FMR1 regulates translation by binding to

polysomal RNA, the absence of FMR1 in the fragile X cell lines should lead to differences in the abundance of specific polysome-associated RNAs. In this experiment, >35,000 genes were

compared, and 251 showed substantial differences in abundance between the polysomal RNA fractions of the fragile X and control cell lines. A partial comparison of the sets of genes revealed

14 that were identified in both experiments, and could therefore be targets for regulation by FMR1. The second paper reports a biochemical approach to finding the optimal RNA target sequence

for FMR1. After several rounds of selection from a pool of random RNA sequences, Jennifer Darnell _et al_. identified an RNA molecule that bound to FMR1 with high affinity. They then

defined the minimal sequence required for binding, and concluded that FMR1 requires a specific RNA structure called a G quartet, which is present in only a small percentage of transcripts.

They tested 12 such transcripts for binding to FMR1, and found six that bound. So, there is more to find out about the requirements for FMR1 binding, but the presence of a G quartet is a

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PAPERS * Brown, V. et al. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. _Cell_ 107, 477–487 (2001) Article  CAS 

Google Scholar  * Darnell, J. C. et al. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. _Cell_ 107, 489–499 (2001) Article  CAS  Google Scholar

  FURTHER READING * Chelly, J. & Mandel, J.-L. Monogenic causes of X-linked mental retardation. _Nature Rev. Genet._ 2, 669–680 (2001) Article  CAS  Google Scholar  Download references

Authors * Mark Patterson View author publications You can also search for this author inPubMed Google Scholar RELATED LINKS RELATED LINKS WEB SITES Stephen Warren's lab Robert

Darnell's lab RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Patterson, M. Twin-track approach to fragile X. _Nat Rev Genet_ 3, 4 (2002).

https://doi.org/10.1038/nrg719 Download citation * Issue Date: 01 January 2002 * DOI: https://doi.org/10.1038/nrg719 SHARE THIS ARTICLE Anyone you share the following link with will be able

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