The goal of this application is to uncover the sequences and factors involved in the regulation of the formation and function of the unusually large 3' untranslated region of the MeCP2 gene. This approximately 8.5 kb 3' UTR likely contains elements that regulate gene expression at the post-transcriptional level. First, the investigators will identify auxiliary regulatory elements and factors that play a role in alternative polyadenylation of the MeCP2 gene, the process that determines the size of the 3' UTR in a tissue- and developmental-specific fashion. Second, they will test the hypothesis that the long 3' UTR plays a role in determining differential stability or translation of the MeCP2 mRNA. These studies represent under-explored areas of MeCP2 expression that may have a critical influence in the tissue-specific effects observed in Rett syndrome.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD042464-02
Application #
6629439
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Oster-Granite, Mary Lou
Project Start
2002-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$77,750
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Biochemistry
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
Newnham, Catherine M; Hall-Pogar, Tyra; Liang, Songchun et al. (2010) Alternative polyadenylation of MeCP2: Influence of cis-acting elements and trans-acting factors. RNA Biol 7:361-72
Liang, Songchun; Lutz, Carol S (2006) p54nrb is a component of the snRNP-free U1A (SF-A) complex that promotes pre-mRNA cleavage during polyadenylation. RNA 12:111-21
Pan, Zhenhua; Zhang, Haibo; Hague, Lisa K et al. (2006) An intronic polyadenylation site in human and mouse CstF-77 genes suggests an evolutionarily conserved regulatory mechanism. Gene 366:325-34
Tian, Bin; Hu, Jun; Zhang, Haibo et al. (2005) A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res 33:201-12