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miR-181b negatively regulates activation-induced cytidine deaminase in B cells

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...

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Autores principales: de Yébenes, Virginia G., Belver, Laura, Pisano, David G., González, Susana, Villasante, Aranzazu, Croce, Carlo, He, Lin, Ramiro, Almudena R.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556787/
https://www.ncbi.nlm.nih.gov/pubmed/18762567
http://dx.doi.org/10.1084/jem.20080579
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author de Yébenes, Virginia G.
Belver, Laura
Pisano, David G.
González, Susana
Villasante, Aranzazu
Croce, Carlo
He, Lin
Ramiro, Almudena R.
author_facet de Yébenes, Virginia G.
Belver, Laura
Pisano, David G.
González, Susana
Villasante, Aranzazu
Croce, Carlo
He, Lin
Ramiro, Almudena R.
author_sort de Yébenes, Virginia G.
collection PubMed
description 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.
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spelling pubmed-25567872009-03-29 miR-181b negatively regulates activation-induced cytidine deaminase in B cells de Yébenes, Virginia G. Belver, Laura Pisano, David G. González, Susana Villasante, Aranzazu Croce, Carlo He, Lin Ramiro, Almudena R. J Exp Med Brief Definitive Reports 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. The Rockefeller University Press 2008-09-29 /pmc/articles/PMC2556787/ /pubmed/18762567 http://dx.doi.org/10.1084/jem.20080579 Text en © 2008 de Yébenes et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Reports
de Yébenes, Virginia G.
Belver, Laura
Pisano, David G.
González, Susana
Villasante, Aranzazu
Croce, Carlo
He, Lin
Ramiro, Almudena R.
miR-181b negatively regulates activation-induced cytidine deaminase in B cells
title miR-181b negatively regulates activation-induced cytidine deaminase in B cells
title_full miR-181b negatively regulates activation-induced cytidine deaminase in B cells
title_fullStr miR-181b negatively regulates activation-induced cytidine deaminase in B cells
title_full_unstemmed miR-181b negatively regulates activation-induced cytidine deaminase in B cells
title_short miR-181b negatively regulates activation-induced cytidine deaminase in B cells
title_sort mir-181b negatively regulates activation-induced cytidine deaminase in b cells
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556787/
https://www.ncbi.nlm.nih.gov/pubmed/18762567
http://dx.doi.org/10.1084/jem.20080579
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