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

Item Type:Article
Title:MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation
Creators Name:Dorsett, Y., McBride, K.M., Jankovic, M., Gazumyan, A., Thai, T.H., Robbiani, D.F., Di Virgilio, M., Reina San-Martin, B., Heidkamp, G., Schwickert, T.A., Eisenreich, T., Rajewsky, K. and Nussenzweig, M.C.
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.
Keywords:3' Untranslated Regions, B-Lymphocytes, Cytidine Deaminase, Genetic Translocation, Immunoglobulin Class Switching, Immunoglobulin Genes, Immunoglobulin Heavy Chains, Immunoglobulin Somatic Hypermutation , Lipopolysaccharides, Messenger RNA , MicroRNAs, Mutation, myc Genes , RNA Stability, Animals, Mice
Publisher:Cell Press
Page Range:630-638
Date:16 May 2008
Official Publication:https://doi.org/10.1016/j.immuni.2008.04.002
PubMed:View item in PubMed

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