A complex pattern of evolutionary conservation and alternative polyadenylation within the long 3 '-untranslated region of the methyl-CpG-binding protein 2 gene (MeCP2) suggests a regulatory role in gene expression

A systematic search for expressed sequences in the human Xq28 region result ed in the isolation of 8.5 kb large contigs of human and murine cDNAs with no apparent conserved open reading frames. These cDNAs were found to be der ived from the 3'-untranslated region (3'-UTR) of the methyl-CpG-binding pro tein 2 gene (MeCP2). This long 3'-UTR is part of an alternatively polyadeny lated, 10.1 kb MeCP2 transcript which is differentially expressed in human brain and other tissues. RNA in situ hybridization to sections of mouse emb ryo and adult tissues of an Mecp2 3'-UTR probe showed ubiquitous low level expression in early organogenesis and enhanced expression in the hippocampu s during formation of the differentiated brain. Sequence comparison between the human and mouse homologues revealed several blocks of very high conser vation separated by less conserved sequences. Additional support for a doma in-like conservation pattern of the long 3'-UTR of the MeCP2 gene was obtai ned by examining conservation in the chimpanzee, orangutan, macaque, hamste r, rat and kangaroo, The minimum free energy distribution for the predicted RNA secondary structure was very similar in human and mouse sequences. In particular, the conserved blocks were predicted to be of high minimum free energy, which suggests weak secondary structure with respect to RNA folding . The fact that both the sequence and predicted secondary structure have be en highly conserved during evolution suggests that both the primary sequenc e and the three-dimensional structure of the 3'-UTR may be important for it s function in post-transcriptional regulation of MeCP2 expression.