Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress

Kishore B. Challagundla, Xiao Xin Sun, Xiaoli Zhang, Tiffany DeVine, Qinghong Zhang, Rosalie C. Sears, Mu Shui Dai

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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 stressinducing 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.

Original languageEnglish (US)
Pages (from-to)4007-4021
Number of pages15
JournalMolecular and cellular biology
Volume31
Issue number19
DOIs
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress'. Together they form a unique fingerprint.

  • Cite this