Mol Cell Biol 2011,
PMID: 21807902
Challagundla, Kishore B; Sun, Xiao-Xin; Zhang, Xiaoli; DeVine, Tiffany; Zhang, Qinghong; Sears, Rosalie C; Dai, Mu-Shui
c-Myc promotes cell growth by enhancing ribosomal biogenesis and translation. Deregulated expression of c-Myc and aberrant ribosomal biogenesis and translation contribute to tumorigenesis. Thus, a fine coordination between c-Myc and ribosomal biogenesis is vital for normal cell homeostasis. Here, we show that ribosomal protein L11 regulates c-myc mRNA turnover. L11 binds to c-myc mRNA at its 3' untranslated region (3'-UTR), the core component of microRNA-induced silencing complex (miRISC) argonaute 2 (Ago2), as well as miR-24, leading to c-myc mRNA reduction. Knockdown of L11 drastically increases the levels and stability of c-myc mRNA. Ablation of Ago2 abrogated the L11-mediated reduction of c-myc mRNA, whereas knockdown of L11 rescued miR-24-mediated c-myc mRNA decay. Interestingly, treatment of cells with the ribosomal stress-inducing agent actinomycin D or 5-fluorouracil significantly decreased the c-myc mRNA levels in an L11- and Ago2-dependent manner. Both treatments enhanced the association of L11 with Ago2, miR-24, and c-myc mRNA. We further show that ribosome-free L11 binds to c-myc mRNA in the cytoplasm and that this binding is enhanced by actinomycin D treatment. Together, our results identify a novel regulatory paradigm wherein L11 plays a critical role in controlling c-myc mRNA turnover via recruiting miRISC in response to ribosomal stress.
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Text Mining Data
c-Myc ⊣ miR-24/miRISC: "
Ribosomal protein L11 recruits
miR-24/miRISC to
repress c-Myc expression in response to ribosomal stress
"
mRNA decay → miR-24: "
Ablation of Ago2 abrogated the L11 mediated reduction of c-myc mRNA, whereas knockdown of L11 rescued miR-24 mediated c-myc mRNA decay
"
Manually curated Databases
No curated data.