3’UTR Shortening Potentiates MicroRNA-Based Repression of Pro-differentiation Genes in Proliferating Human Cells
(A) A pro-proliferation and a pro-differentiation genes are shown, each being subject to a different miRNA. The pro-proliferation gene contains the miRNA binding site close to the full-length 3’ UTR (near the polyadenylation (PA) site, while the pro-differentiation gene contains its site in the middle of the full-length 3’ UTR, yet immediately upstream to an APA site. The left side represents a differentiated lowly proliferative tissue, in which both genes mainly feature the long UTR. Under this condition the pro-proliferation gene is repressed while the pro-differentiation gene is free from repression. On the right side the cells are proliferative and the 3’ UTRs of the two genes are shortened. In this condition the pro-proliferation gene is relieved from repression since the binding site no longer exists in its UTR. In contrast, the pro-differentiation gene now becomes subject to increased repression since its binding site now becomes closer to the new UTR end. (B-F) Conserved and non-conserved miRNA binding sites around the APA site (point 0), for all genes with at least 1000 bases of 3’ UTR sequence from each side of the APA site, in different cell lines: WI38 (B), U2OS (C), BJ (D), MCF10A (E) and Mouse Muscle Tissue (Genes with at least 5000 bases 3’ UTR sequences from each side of the APA site) (F). * indicates p-value<0.05.