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

Abstract : MicroRNAs (miRNAs) are small noncoding RNAs that regulate vast networks of genes that share miRNA target sequences. To examine the physiologic effects of an individual miRNA-mRNA interaction in vivo, we generated mice that carry a mutation in the putative microRNA-155 (miR-155) binding site in the 3'-untranslated region of activation-induced cytidine deaminase (AID), designated Aicda(155) mice. AID is required for immunoglobulin gene diversification in B lymphocytes, but it also promotes chromosomal translocations. Aicda(155) caused an increase in steady-state Aicda mRNA and protein amounts by increasing the half-life of the mRNA, resulting in a high degree of Myc-Igh translocations. A similar but more pronounced translocation phenotype was also found in miR-155-deficient mice. Our experiments indicate that miR-155 can act as a tumor suppressor by reducing potentially oncogenic translocations generated by AID.
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Submitted on : Tuesday, February 3, 2009 - 2:25:06 PM
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yair Dorsett, Kevin M. Mcbride, Mila Jankovic, Anna Gazumyan, To-Ha Thai, et al.. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation.. Immunity, Elsevier, 2008, 28 (5), pp.630-8. ⟨10.1016/j.immuni.2008.04.002⟩. ⟨inserm-00350863⟩



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