? ? MicroRNAs (miRNAs) are small (~22-nucleotide), regulatory RNAs. miRNAs assemble with proteins into microRiboNucleoProteins (microRNPs, -miRNPs-) and control gene expression by base pairing with cognate mRNA targets. miRNAs regulate numerous genes. Most mammalian miRNAs are thought to repress the translation of their target mRNAs. However, the factors and mechanisms that mediate miRNA-directed translational repression are unknown. Recently, the Fragile X mental retardation protein (FMRP) was shown to be associated with miRNAs. Reduced protein levels or loss of function mutations of FMRP cause Fragile X, the most common form of inherited mental retardation. FMRP is an RNA binding protein that is capable of repressing mRNA translation, although its precise molecular function remains elusive. I hypothesize that FMRP and its homologs (FXR1P and FXR2P, -FXRPs-) function in mammalian miRNA-mediated gene expression regulation. I propose to: (1) Characterize mammalian FMRP and FXRP containing miRNPs and the role of FMRP and FXRPs in miRNA function; and (2) Identify the factors that mediate mammalian miRNA-directed translational repression. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30NS054396-01
Application #
7055708
Study Section
Special Emphasis Panel (ZNS1-SRB-M (24))
Program Officer
Riddle, Robert D
Project Start
2006-04-01
Project End
2009-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$39,472
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Liu, Xuhang; Fortin, Kristine; Mourelatos, Zissimos (2008) MicroRNAs: biogenesis and molecular functions. Brain Pathol 18:113-21