Enhancer regulation of polyadenylation. Homo sapiens

Extensive cancer-specific polyadenylation (poly[A]) site choice is observed in cancer, leading to cancer progression promoting changes in protein isoform generation and miRNA binding sites. We find that aberrant cancer-specific intragenic enhancer activity contributes to this abnormal polyadenylation. Modulation of canonical Wnt responsive intragenic enhancer activity causes changes in local poly(A) utilization, controlling key cell cycle regulatory genes. Further, increased cancer-specific local poly(A) utilization occurs around, and is associated with intragenic enhancers gained in cancer.