The RNA Exosome Targets the AID Cytidine Deaminase to Both Strands of Transcribed Duplex DNA Substrates | Zendy

Uttiya Basu | Zendy; FeiLong Meng | Zendy; Celia Keim | Zendy; Veronika Grinstein | Zendy; Evangelos Pefanis | Zendy; Jennifer Eccleston | Zendy; Tingting Zhang | Zendy; Darienne R. Myers | Zendy; Caitlyn R. Wasserman | Zendy; Duane R. Wesemann | Zendy; Kurt Januszyk | Zendy; Richard I. Gregory | Zendy; Haiteng Deng | Zendy; Christopher D. Lima | Zendy; Frederick W. Alt | Zendy

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The RNA Exosome Targets the AID Cytidine Deaminase to Both Strands of Transcribed Duplex DNA Substrates

Author(s) -

Uttiya Basu,

FeiLong Meng,

Celia Keim,

Veronika Grinstein,

Evangelos Pefanis,

Jennifer Eccleston,

Tingting Zhang,

Darienne R. Myers,

Caitlyn R. Wasserman,

Duane R. Wesemann,

Kurt Januszyk,

Richard I. Gregory,

Haiteng Deng,

Christopher D. Lima,

Frederick W. Alt

Publication year - 2011

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2011.01.001

Subject(s) - cytidine deaminase , biology , somatic hypermutation , rna , activation induced (cytidine) deaminase , dna , microbiology and biotechnology , rna editing , transcription (linguistics) , immunoglobulin class switching , non coding rna , exosome complex , genetics , gene , antibody , b cell , linguistics , philosophy

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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