Format

Send to

Choose Destination
Cell. 2015 May 7;161(4):762-73. doi: 10.1016/j.cell.2015.03.020.

Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA.

Author information

1
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.
2
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.
3
Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
4
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.

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.

PMID:
25957684
PMCID:
PMC4426339
DOI:
10.1016/j.cell.2015.03.020
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center