1. Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA.
- Author
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Zheng S, Vuong BQ, Vaidyanathan B, Lin JY, Huang FT, and Chaudhuri J
- Subjects
- Animals, G-Quadruplexes, Introns, Maltose-Binding Proteins metabolism, Mice, RNA Processing, Post-Transcriptional, RNA, Guide, CRISPR-Cas Systems, Cytidine Deaminase metabolism, Immunoglobulin Class Switching
- Abstract
Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to target AID to S region DNA. AID binds directly to switch RNA through G-quadruplexes formed by the RNA molecules. Disruption of this interaction by mutation of a key residue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR. Additionally, inhibition of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression of switch transcripts in a sequence-specific manner. These studies uncover an RNA-mediated mechanism of targeting AID to DNA., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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