MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation.
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.
Dorsett
Yair
Y
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
McBride
Kevin M
KM
Jankovic
Mila
M
Gazumyan
Anna
A
Thai
To-Ha
TH
Robbiani
Davide F
DF
Di Virgilio
Michela
M
Reina San-Martin
Bernardo
B
Heidkamp
Gordon
G
Schwickert
Tanja A
TA
Eisenreich
Thomas
T
Rajewsky
Klaus
K
Nussenzweig
Michel C
MC
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)
D020413:3' Untranslated Regions; D007143:Immunoglobulin Heavy Chains; D008070:Lipopolysaccharides; D035683:MicroRNAs; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase