Fragile X syndrome, the most common form of inheritable mental retardation, results from the loss of function of the fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein shown to effect the translation and translocation of mRNA in the brain. Recently, FMRP has been shown to associate with the microRNA pathway. However, the molecular mechanisms controlling the activity of FMRP to effect translation remain elusive.
The aims of this proposal are: 1) to determine the effects of FMRP on the expression levels of microRNA, and in particular let-7b, during brain development and 2) to determine the existence of a coordinated role of microRNA and FMRP to suppress translation. To examine these aims, MAPI B will be used as the experimental model due to preliminary data showing that both FMRP and microRNA can regulate the protein levels of MAP1B in the brain. By determining these mechanisms, a clearer understanding and potential, novel therapeutic targets of fragile X syndrome will be obtained, along with an improved understanding of FMRP's role in normal brain development. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS056532-02
Application #
7276137
Study Section
Special Emphasis Panel (ZRG1-F03A-M (20))
Program Officer
Riddle, Robert D
Project Start
2006-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$28,172
Indirect Cost
Name
Emory University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Lau, Anthony G; Irier, Hasan A; Gu, Jiaping et al. (2010) Distinct 3'UTRs differentially regulate activity-dependent translation of brain-derived neurotrophic factor (BDNF). Proc Natl Acad Sci U S A 107:15945-50