Non-coding RNA generated following lariat debranching mediates targeting of AID to DNA Journal Article

Authors: Zheng, S.; Vuong, B. Q.; Vaidyanathan, B.; Lin, J. Y.; Huang, F. T.; Chaudhuri, J.
Article Title: Non-coding RNA generated following lariat debranching mediates targeting of AID to DNA
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. © 2015 Elsevier Inc.
Keywords: controlled study; unclassified drug; mutation; nonhuman; animal cell; mouse; rna; activation induced cytidine deaminase; dna; untranslated rna; rna binding; guanine quadruplex; enzyme; priority journal; article; lariat debranching enzyme
Journal Title: Cell
Volume: 161
Issue: 4
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2015-05-07
Start Page: 762
End Page: 773
Language: English
DOI: 10.1016/j.cell.2015.03.020
PROVIDER: scopus
PMCID: PMC4426339
PUBMED: 25957684
Notes: Export Date: 3 June 2015 -- Source: Scopus
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MSK Authors
  1. Bao Q Vuong
    9 Vuong
  2. Simin Zheng
    4 Zheng