| Literature DB >> 21255825 |
Uttiya Basu1, Fei-Long Meng, Celia Keim, Veronika Grinstein, Evangelos Pefanis, Jennifer Eccleston, Tingting Zhang, Darienne Myers, Caitlyn R Wasserman, Duane R Wesemann, Kurt Januszyk, Richard I Gregory, Haiteng Deng, Christopher D Lima, Frederick W Alt.
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.Entities:
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Year: 2011 PMID： 21255825 PMCID： PMC3065114 DOI： 10.1016/j.cell.2011.01.001
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582