Document Detail


MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase.
MedLine Citation:
PMID:  18450484     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Grace Teng; Paul Hakimpour; Pablo Landgraf; Amanda Rice; Thomas Tuschl; Rafael Casellas; F Nina Papavasiliou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2008-05-01
Journal Detail:
Title:  Immunity     Volume:  28     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-16     Completed Date:  2008-07-07     Revised Date:  2011-12-13    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  621-9     Citation Subset:  IM    
Affiliation:
Laboratory of Lymphocyte Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions
Animals
B-Lymphocytes / enzymology*,  immunology,  metabolism
Cells, Cultured
Cytidine Deaminase / genetics*,  metabolism*
Immunoglobulin Class Switching
Lipopolysaccharides / immunology
Mice
Mice, Mutant Strains
Mice, Transgenic
MicroRNAs / genetics,  immunology,  metabolism*
Mutation
RNA, Messenger / genetics,  metabolism
Somatic Hypermutation, Immunoglobulin
Grant Support
ID/Acronym/Agency:
CA098495/CA/NCI NIH HHS; GM066699/GM/NIGMS NIH HHS; R01 CA098495-05/CA/NCI NIH HHS; R01 CA098495-09/CA/NCI NIH HHS; Z01 AR041149-03/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/Lipopolysaccharides; 0/MicroRNAs; 0/RNA, Messenger; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase
Comments/Corrections
Comment In:
Immunity. 2008 May;28(5):596-8   [PMID:  18482561 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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