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Cell. 2011 Feb 4;144(3):353-63. doi: 10.1016/j.cell.2011.01.001. Epub 2011 Jan 20.

The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates.

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1
Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Immune Disease Institute, Children's Hospital Boston, Department of Genetics, Harvard Medical School, MA 02115, USA. ub2121@columbia.edu

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.

PMID:
21255825
PMCID:
PMC3065114
DOI:
10.1016/j.cell.2011.01.001
[Indexed for MEDLINE]
Free PMC Article
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