Fragile X mental retardation syndrome is the most common form of inherited mental retardation. It is transmitted as a X-linked dominant trait with reduced penetrance and is associated with a fragile site known as FRAXA (Fragile site, X chromosome, A site) at Xq27.3. The pathogenesis of fragile X syndrome is thought to be due to a massive trinucleotide repeat expansion in the 5'UTR of the fragile X mental retardation-i gene (FMR1), which results in the loss of its protein product, FMRP. Although the precise function of FMRP has not yet been elucidated, it is believed to be a RNA-binding protein that associates with polyribosomes and the rough endoplasmic reticulum. And because FMRP is translated in the synapse in response to synaptic activation, it has been suggested to play important roles in protein translation and in synaptic plasticity. Interestingly, a growing body of evidence indicates a defect in translational processing of FMR1 as a potential mechanism leading to fragile X syndrome. Presently, however, the mechanism behind the regulation of FMR1 translation is poorly understood. Such understanding is necessary for elucidating the pathogenesis of fragile X syndrome and for identifying potential molecular targets for therapy. Therefore, I will examine the molecular basis behind the regulation and activation of FMR1 translation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH065094-05
Application #
7086178
Study Section
Special Emphasis Panel (ZRG1-F03A (21))
Program Officer
Curvey, Mary F
Project Start
2002-07-01
Project End
2007-05-31
Budget Start
2006-07-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$42,682
Indirect Cost
Name
Brown University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Lim, Jae H; Booker, Anne B; Luo, Ting et al. (2005) AP-2alpha selectively regulates fragile X mental retardation-1 gene transcription during embryonic development. Hum Mol Genet 14:2027-34
Lim, Jae H; Booker, Anne B; Fallon, Justin R (2005) Regulating fragile X gene transcription in the brain and beyond. J Cell Physiol 205:170-5
Lim, Jae H; Luo, Ting; Sargent, Thomas D et al. (2005) Developmental expression of Xenopus fragile X mental retardation-1 gene. Int J Dev Biol 49:981-4