Regulating infidelity: RNA-mediated recruitment of AID to DNA during class switch recombination

Eur J Immunol. 2016 Mar;46(3):523-30. doi: 10.1002/eji.201545809. Epub 2016 Feb 22.

Abstract

The mechanism by which the DNA deaminase activation-induced cytidine deaminase (AID) is specifically recruited to repetitive switch region DNA during class switch recombination is still poorly understood. Work over the past decade has revealed a strong link between transcription and RNA polymerase-associated factors in AID recruitment, yet none of these processes satisfactorily explain how AID specificity is affected. Here, we review a recent finding wherein AID is guided to switch regions not by a protein factor but by an RNA moiety, and especially one associated with a noncoding RNA that has been long thought of as being inert. This work explains the long-standing requirement of splicing of noncoding transcripts during class switching, and has implications in both B cell-mediated immunity as well as the underlying pathological syndromes associated with the recombination reaction.

Keywords: AID; Class switch recombination; Immunoglobulin; Noncoding/intronic RNA; Switch region.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • DNA / metabolism*
  • Humans
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin Switch Region / genetics
  • Immunoglobulins / genetics
  • Mice
  • RNA / genetics
  • RNA / physiology*
  • Recombination, Genetic

Substances

  • Immunoglobulins
  • RNA
  • DNA
  • Cytidine Deaminase