The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates.
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.
Mesh Terms:
Animals, B-Lymphocytes, Cell Line, Cells, Cultured, Cytidine Deaminase, Exoribonucleases, Humans, Immunoglobulin Class Switching, Immunoglobulin Heavy Chains, Mice, Multienzyme Complexes, RNA, Transcription, Genetic
Animals, B-Lymphocytes, Cell Line, Cells, Cultured, Cytidine Deaminase, Exoribonucleases, Humans, Immunoglobulin Class Switching, Immunoglobulin Heavy Chains, Mice, Multienzyme Complexes, RNA, Transcription, Genetic
Cell
Date: Feb. 04, 2011
PubMed ID: 21255825
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