The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates Journal Article
| Authors: | Basu, U.; Meng, F. L.; Keim, C.; Grinstein, V.; Pefanis, E.; Eccleston, J.; Zhang, T.; Myers, D.; Wasserman, C. R.; Wesemann, D. R.; Januszyk, K.; Gregory, R. I.; Deng, H.; Lima, C. D.; Alt, F. W. |
| Article Title: | The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates |
| 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. © 2011 Elsevier Inc. |
| Journal Title: | Cell |
| Volume: | 144 |
| Issue: | 3 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2011-02-04 |
| Start Page: | 353 |
| End Page: | 363 |
| Language: | English |
| DOI: | 10.1016/j.cell.2011.01.001 |
| PROVIDER: | scopus |
| PMCID: | PMC3065114 |
| PUBMED: | 21255825 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: CELLB" - "Source: Scopus" |
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