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.
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