3’UTR Shortening Potentiates MicroRNA-Based Repression of Pro-differentiation Genes in Proliferating Human Cells
Two genes, Gene 1 and Gene 2 contain a binding site for same miRNA and are hence potentially subject to its regulation. In one physiological condition (A) the two genes feature mostly the long 3’ UTR, and as the binding site is close to its center, the miRNA can exert little to none of its regulatory effect on the two genes. Upon switch to the second condition (B), Expression of the miRNA is induced. In that condition, Gene 1 undergoes 3’ UTR shortening and its binding site now becomes closer to the UTR’s end, while Gene 2 remains unmodified. Hence, Gene 1, but not Gene 2, now becomes fully accessible to repression by the induced miRNA, and the levels of its short transcript, although upregulated by the shortening, remain low because of the effective targeting of the miRNA. In this way selective 3’ UTR shortening may serve as a dynamic means to differentiate between different targets of the same miRNA, providing the network with additional regulatory flexibility.