title: 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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Dorsett
authors.forename: Kevin M
authors.initials: KM
authors.lastname: McBride
authors.forename: Mila
authors.initials: M
authors.lastname: Jankovic
authors.forename: Anna
authors.initials: A
authors.lastname: Gazumyan
authors.forename: To-Ha
authors.initials: TH
authors.lastname: Thai
authors.forename: Davide F
authors.initials: DF
authors.lastname: Robbiani
authors.forename: Michela
authors.initials: M
authors.lastname: Di Virgilio
authors.forename: Bernardo
authors.initials: B
authors.lastname: Reina San-Martin
authors.forename: Gordon
authors.initials: G
authors.lastname: Heidkamp
authors.forename: Tanja A
authors.initials: TA
authors.lastname: Schwickert
authors.forename: Thomas
authors.initials: T
authors.lastname: Eisenreich
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D020413:3' Untranslated Regions; D007143:Immunoglobulin Heavy Chains; D008070:Lipopolysaccharides; D035683:MicroRNAs; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase