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

Abstract

In this funding period, we have discovered that L11 downregulates c-myc mRNA through a mircoRNA-mediated pathway. L11 binds to c-myc mRNA at its 3'-untranslated region (3?-UTR), the core component of microRNA-induced silencing complex (miRISC) 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 the miR-24-mediated c-myc mRNA decay. We further show that ribosome-free L11 binds to c-myc mRNA in the cytoplasm and this binding is enhanced in response to ribosomal stress. Meanwhile, we found that c-myc is also down-regulated in response to DNA damage including UV and gamma-irradiation (gamma-IR) in an L11-dependent manner. Altogether, 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 stress.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2011
Accession Number
ADA555902

Entities

People

  • Mu-Shui Dai

Organizations

  • Oregon Health & Science University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytoplasm
  • Degradation
  • Enzyme Inhibitors
  • Gene Expression
  • Genes
  • Genetics
  • Neoplasms
  • Organelles
  • Proteins
  • Recruiting
  • Regulations
  • Rna Stability

Fields of Study

  • Biology

Readers

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  • Molecular Genetics
  • Nuclear and Radiation Engineering.