Figure 4.

Conserved 3′-UTR cis-regulatory elements map of MECP2 mRNA orthologs and isoforms. Majority of the cis-regulatory elements mapped to the evolutionarily conserved regions of long MECP2 isoform 3′-UTR which is involved in early brain development. All four mammalian orthologs of MECP2 mRNAs from human, dog, mouse, and rat were analyzed. Only human and mouse mRNA alignments are displayed. Human MECP2 alignments with its dog and rat orthologs were very similar to the alignment shown. The short human MECP2 isoform 2 lacked conserved microRNA targets, ARE, or G-quadruplexes. A highly conserved G-quadruplex is present selectively near one alternative polyadenylation signal/site. Most evolutionarily conserved G-quadruplexes were preferentially associated with microRNA target sites. Evolutionarily conserved AU-rich element (ARE) and mi-R148/152 target sites were associated with the second alternative poly(A) site which results in the expression of longer isoform during the early development of the human brain.