| First Author | de Yébenes VG | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 10 | Pages | 2199-206 |
| PubMed ID | 18762567 | Mgi Jnum | J:141184 |
| Mgi Id | MGI:3817382 | Doi | 10.1084/jem.20080579 |
| Citation | de Yebenes VG, et al. (2008) miR-181b negatively regulates activation-induced cytidine deaminase in B cells. J Exp Med 205(10):2199-206 |
| abstractText | Activated B cells reshape their primary antibody repertoire after antigen encounter by two molecular mechanisms: somatic hypermutation (SHM) and class switch recombination (CSR). SHM and CSR are initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues on the immunoglobulin loci, which leads to the generation of DNA mutations or double-strand break intermediates. As a bystander effect, endogenous AID levels can also promote the generation of chromosome translocations, suggesting that the fine tuning of AID expression may be critical to restrict B cell lymphomagenesis. To determine whether microRNAs (miRNAs) play a role in the regulation of AID expression, we performed a functional screening of an miRNA library and identified miRNAs that regulate CSR. One such miRNA, miR-181b, impairs CSR when expressed in activated B cells, and results in the down-regulation of AID mRNA and protein levels. We found that the AID 3' untranslated region contains multiple putative binding sequences for miR-181b and that these sequences can be directly targeted by miR-181b. Overall, our results provide evidence for a new regulatory mechanism that restricts AID activity and can therefore be relevant to prevent B cell malignant transformation. |
