MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation

Yair Dorsett1, Kevin M McBride, Mila Jankovic

  • 1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

Immunity
|May 6, 2008
PubMed

Insights

MicroRNA-155 (miR-155) acts as a tumor suppressor by regulating activation-induced cytidine deaminase (AID). This microRNA reduces potentially oncogenic translocations in vivo, highlighting its role in preventing cancer.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression through target sequences.
  • Activation-induced cytidine deaminase (AID) is crucial for immunoglobulin gene diversification but also induces chromosomal translocations.
  • Understanding specific miRNA-mRNA interactions in vivo is essential for elucidating physiological roles.

Purpose of the Study:

  • To investigate the physiological impact of the microRNA-155 (miR-155) binding site within the activation-induced cytidine deaminase (AID) mRNA.
  • To determine the role of miR-155 in regulating AID expression and its downstream consequences on chromosomal translocations.

Main Methods:

  • Generation of Aicda(155) mutant mice with a disrupted miR-155 binding site in the AID 3'-untranslated region.
  • Analysis of AID mRNA and protein levels, including mRNA half-life.
  • Assessment of Myc-Igh translocation frequency in Aicda(155) mice and miR-155-deficient mice.

Main Results:

  • The Aicda(155) mutation led to increased steady-state AID mRNA and protein levels due to enhanced mRNA stability.
  • A high frequency of Myc-Igh translocations was observed in Aicda(155) mice.
  • miR-155-deficient mice exhibited a more pronounced translocation phenotype compared to Aicda(155) mice.

Conclusions:

  • miR-155 negatively regulates AID expression by targeting its mRNA, thereby controlling AID-induced translocations.
  • miR-155 functions as a tumor suppressor by mitigating the generation of potentially oncogenic translocations mediated by AID.
  • This study elucidates a critical mechanism by which miR-155 contributes to genomic stability in B lymphocytes.

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