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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.

Pubmed ID: 21255825

Authors

  • Basu U
  • Meng FL
  • Keim C
  • Grinstein V
  • Pefanis E
  • Eccleston J
  • Zhang T
  • Myers D
  • Wasserman CR
  • Wesemann DR
  • Januszyk K
  • Gregory RI
  • Deng H
  • Lima CD
  • Alt FW

Journal

Cell

Publication Data

February 4, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI31541
  • Agency: NCI NIH HHS, Id: CA09503-23
  • Agency: NIGMS NIH HHS, Id: GM079196
  • Agency: NIAID NIH HHS, Id: P01 AI031541
  • Agency: NIAID NIH HHS, Id: R01 AI077595
  • Agency: NIAID NIH HHS, Id: R01 AI077595-04
  • Agency: NIGMS NIH HHS, Id: R01 GM079196
  • Agency: NIGMS NIH HHS, Id: R01 GM079196-01A1
  • Agency: NIGMS NIH HHS, Id: R01 GM079196-02
  • Agency: NIGMS NIH HHS, Id: R01 GM079196-03
  • Agency: NIGMS NIH HHS, Id: R01 GM079196-04

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