Regulation of c-Myc mRNA by L11 in Response to UV and Gamma Irradiation.

摘要

During the funding period, we first discovered that L11 recruits miR-24-loaded miRISC to the c-myc mRNA 3'-UTR to induce c-myc mRNA decay in response to ribosomal stress. We then found that L11 also suppress c-myc expression in response to UV irradiation-induced DNA damage by recruiting miR-130a-miRISC to the c-myc mRNA 3'-UTR, thereby destabilizing c-myc mRNA. We showed that miR-130a directly targets c-myc mRNA. Overexpression of miR-130a reduced the levels of c-myc mRNA whereas inhibiting miR-130a drastically induced the levels of c-myc mRNA. Overexpression of miR-130a increased the association of Ago2/miRISC with c-myc mRNA. Interestingly, UV treatment enhances the association of L11, Ago2 as well as miR-130a with the c-myc mRNA. Inhibiting miR-130a significantly suppresses UV-mediated c-Myc reduction. Together, our results reveal a novel regulatory paradigm wherein L11 plays a key role in controlling c-myc mRNA turnover in response to stress via targeting c-myc mRNAby miR-24 and miR-130a. Our results also imply that miR-130a and miR-24 may possesses a tumor suppressor function through down regulating c-Myc.