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

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

  • Cell. 2011 Feb 4;144(3):353-63. doi: 10.1016/j.cell.2011.01.001.
Uttiya Basu 1,  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
Affiliations

Affiliation

  • 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
PMID: 21255825 DOI: 10.1016/j.cell.2011.01.001
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.

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