MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase.
B lymphocytes perform somatic hypermutation and class-switch recombination (CSR) of the immunoglobulin locus to generate an antibody repertoire diverse in both affinity and function. These somatic diversification processes are catalyzed by activation-induced cytidine deaminase (AID), a potent DNA mutator whose expression and function are highly regulated. Here we show that AID was regulated posttranscriptionally by a lymphocyte-specific microRNA, miR-155. We found that miR-155 was upregulated in murine B lymphocytes undergoing CSR and that it targeted a conserved site in the 3'-untranslated region of the mRNA encoding AID. Disruption of this target site in vivo resulted in quantitative and temporal deregulation of AID expression, along with functional consequences for CSR and affinity maturation. Thus, miR-155, which has recently been shown to play important roles in regulating the germinal-center reaction, does so in part by directly downmodulating AID expression.
Teng
Grace
G
Laboratory of Lymphocyte Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Hakimpour
Paul
P
Landgraf
Pablo
P
Rice
Amanda
A
Tuschl
Thomas
T
Casellas
Rafael
R
Papavasiliou
F Nina
FN
D020413:3' Untranslated Regions; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D020413:3' Untranslated Regions; D008070:Lipopolysaccharides; D035683:MicroRNAs; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase