| First Author | Ribeiro de Almeida C | Year | 2018 |
| Journal | Mol Cell | Volume | 70 |
| Issue | 4 | Pages | 650-662.e8 |
| PubMed ID | 29731414 | Mgi Jnum | J:261976 |
| Mgi Id | MGI:6159324 | Doi | 10.1016/j.molcel.2018.04.001 |
| Citation | Ribeiro de Almeida C, et al. (2018) RNA Helicase DDX1 Converts RNA G-Quadruplex Structures into R-Loops to Promote IgH Class Switch Recombination. Mol Cell 70(4):650-662.e8 |
| abstractText | 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. |
