Divergence of alternative polyadenylation in mouse

Alternative polyadenylation (APA), which is regulated by both cis-elements and trans-factors, plays an important role in post-transcriptional regulation of eukaryotic gene expression through generating diverse RNA isoforms. However, comparing to gene expression and alternative splicing, the regulatory pattern of APA and the relative contribution from cis- and trans-effect on APA during evolution are still unclear. Here by using deep sequencing based method and a hybrid mouse system including C57BL/6J, SPRET/EiJ, and their F1 hybrids, we investigated the pAs divergence between the two parental strains and that between two alleles of their F1 hybrids. Among the 24721 pAs from 7271 genes expressing multiple pAs, we identified 3747 pAs showed significant divergence between the two strains and observed a predominant contribution of cis-regulatory effect on pAs usage by integrating allelic specific data of F1 hybrids across all five types of APA. Systematic analysis of the sequence features in proximity to the cis-divergent pAs revealed that the local RNA secondary structure and presence of a stretch of Us in the upstream region could negatively modulate the pAs usage.