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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. and Dhir, S. and Dhir, A. and Moghaddam, A.E. and Sattentau, Q. and 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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