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.
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Simin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Biology, City College of New York, New York, NY 10031, USA.
authors.forename: Bao Q
authors.initials: BQ
authors.lastname: Vuong
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Vaidyanathan
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Lin
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Feng-Ting
authors.initials: FT
authors.lastname: Huang
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. Electronic address: chaudhuj@mskcc.org.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism*; D054856:G-Quadruplexes; D017578:Immunoglobulin Class Switching; D007438:Introns; D058619:Maltose-Binding Proteins / Q000378:metabolism; D051379:Mice; D012323:RNA Processing, Post-Transcriptional; D000094704:RNA, Guide, CRISPR-Cas Systems; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D003564:Cytidine Deaminase; D058619:Maltose-Binding Proteins; D000094704:RNA, Guide, CRISPR-Cas Systems; D000098830:AICDA (Activation-Induced Cytidine Deaminase)