The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates.
Cell
; 144(3): 353-63, 2011 Feb 04.
Article
en En
| MEDLINE
| ID: mdl-21255825
ABSTRACT
Activation-induced cytidine deaminase (AID) initiates immunoglobulin (Ig) heavy-chain (IgH) class switch recombination (CSR) and Ig variable region somatic hypermutation (SHM) in B lymphocytes by deaminating cytidines on template and nontemplate strands of transcribed DNA substrates. However, the mechanism of AID access to the template DNA strand, particularly when hybridized to a nascent RNA transcript, has been an enigma. We now implicate the RNA exosome, a cellular RNA-processing/degradation complex, in targeting AID to both DNA strands. In B lineage cells activated for CSR, the RNA exosome associates with AID, accumulates on IgH switch regions in an AID-dependent fashion, and is required for optimal CSR. Moreover, both the cellular RNA exosome complex and a recombinant RNA exosome core complex impart robust AID- and transcription-dependent DNA deamination of both strands of transcribed SHM substrates in vitro. Our findings reveal a role for noncoding RNA surveillance machinery in generating antibody diversity.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN
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Linfocitos B
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Cadenas Pesadas de Inmunoglobulina
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Cambio de Clase de Inmunoglobulina
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Citidina Desaminasa
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Exorribonucleasas
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Complejos Multienzimáticos
Límite:
Animals
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Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article