TY - JOUR
T1 - MicroRNA-155 Suppresses Activation-Induced Cytidine Deaminase-Mediated Myc-Igh Translocation
AU - Dorsett, Yair
AU - McBride, Kevin M.
AU - Jankovic, Mila
AU - Gazumyan, Anna
AU - Thai, To Ha
AU - Robbiani, Davide F.
AU - Di Virgilio, Michela
AU - San-Martin, Bernardo Reina
AU - Heidkamp, Gordon
AU - Schwickert, Tanja A.
AU - Eisenreich, Thomas
AU - Rajewsky, Klaus
AU - Nussenzweig, Michel C.
N1 - Funding Information:
We thank D. Dorsett, M. Dorsett, D. Scheinker for suggestions; K. Velinzon and T. Shengelia for cell sorting; and D. Bosque for animal husbandry. This work was supported by the Schering Foundation (T.A.S.), the Leukemia and Lymphoma Society (D.F.R.), and grants from National Institutes of Health AI064345 (to K.R.) and AI06231 (to M.C.N.). M.C.N is a Howard Hughes Medical Institute investigator.
PY - 2008/5/16
Y1 - 2008/5/16
N2 - 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 Aicda155 mice. AID is required for immunoglobulin gene diversification in B lymphocytes, but it also promotes chromosomal translocations. Aicda155 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.
AB - 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 Aicda155 mice. AID is required for immunoglobulin gene diversification in B lymphocytes, but it also promotes chromosomal translocations. Aicda155 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.
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=43049173617&partnerID=8YFLogxK
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U2 - 10.1016/j.immuni.2008.04.002
DO - 10.1016/j.immuni.2008.04.002
M3 - Article
C2 - 18455451
AN - SCOPUS:43049173617
SN - 1074-7613
VL - 28
SP - 630
EP - 638
JO - Immunity
JF - Immunity
IS - 5
ER -