RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination

Ribeiro de Almeida, C.; Dhir, S.; Dhir, A.; Moghaddam, A.E.; Sattentau, Q.; Meinhart, A.; Proudfoot, N.J.

RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination

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Item Type:	Article
Title:	RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination
Creators Name:	Ribeiro de Almeida, C., Dhir, S., Dhir, A., Moghaddam, A.E., Sattentau, Q., Meinhart, A. and Proudfoot, N.J.
Abstract:	Class switch recombination (CSR) at the immunoglobulin heavy-chain (IgH) locus is associated with the formation of R-loop structures over switch (S) regions. While these often occur co-transcriptionally between nascent RNA and template DNA, we now show that they also form as part of a post-transcriptional mechanism targeting AID to IgH S-regions. This depends on the RNA helicase DDX1 that is also required for CSR in vivo. DDX1 binds to G-quadruplex (G4) structures present in intronic switch transcripts and converts them into S-region R-loops. This in turn targets the cytidine deaminase enzyme AID to S-regions so promoting CSR. Notably R-loop levels over S-regions are diminished by chemical stabilization of G4 RNA or by the expression of a DDX1 ATPase-deficient mutant that acts as a dominant-negative protein to reduce CSR efficiency. In effect, we provide evidence for how S-region transcripts interconvert between G4 and R-loop structures to promote CSR in the IgH locus.
Keywords:	R-Loops, G-Quadruplexes, DEAD-Box RNA Helicase 1, Class Switch Recombination, Activation-Induced Cytidine Deaminase, Animals, Mice
Source:	Molecular Cell
ISSN:	1097-2765
Publisher:	Cell Press
Volume:	70
Number:	4
Page Range:	650-662
Date:	17 May 2018
Official Publication:	https://doi.org/10.1016/j.molcel.2018.04.001
PubMed:	View item in PubMed

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