Regulation of C-Myc mRNA by L11 in Response to UV and Gamma Irradiation
Annual rept. 20 Sep 2012-19 Sep 2013
OREGON HEALTH AND SCIENCES UNIV PORTLAND
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In previous funding years, we have discovered a novel regulatory paradigm wherein L11 plays a critical role in controlling c-myc mRNA turnover via recruiting miR-24-loaded miRISC to the c-myc mRNA 3 -UTR in response to ribosomal stress. We also found that c-myc mRNA is down-regulated in response to DNA damage including UV and -irradiation in a L11-dependent manner. RNA-IP-RNAseq analysis identified that miR-130a as a L11-associated microRNA. We further showed that miR-130a directly targets c-myc mRNA. Overexpression of miR-130a mimics reduced the levels of c-myc mRNA whereas inhibiting miR-130a drastically induced the levels of c-myc mRNA. Also, overexpression of miR-130a reduced the luciferase activity driven by luciferase reporter containing the c-myc 3 -UTR and increased the association of Ago2miRISC with c-myc mRNA. Interestingly, UV treatment enhances the association of L11, Ago2 as well as miR-130a with the c-myc mRNA. Together, our current results suggest that L11 may recruit miR- 130a-loaded miRISC to mediate c-myc decay in response to DNA damage and implying that miR- 130a may possesses a tumor suppressor function through down regulating c-Myc.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research