Recent work has shown that microRNAs, including miR-16, are regulated by and play a role in the DDR and, furthermore, that p53 affects the level of specific microRNAs through transcription-dependent and independent mechanisms (33–35). Specifically, miR-16 expression was found to be induced following DNA damage through p53-dependent promotion of its processing and maturation (34). The mature form of miR-16 binds to the 3′UTR of Wip1 mRNA and promotes its degradation (Figure 3) (36). Expression of miR-16 decreased Wip1 mRNA levels through binding to a 12-base region of the 3′UTR, since the activity of a reporter construct with a mutation in this region was not affected by miR-16 expression. Furthermore, the authors showed that miR-16 inhibits Wip1 expression in a time-dependent manner after exposure to neocarzinostatin (NCS) (36). Thus, miR-16 may negatively regulate Wip1 expression by decreasing Wip1 mRNA stability.
