RNA Helicase DDX1 Converts RNA G-Quadruplex Structures into R-Loops to Promote IgH Class Switch Recombination.
Mol Cell
; 70(4): 650-662.e8, 2018 05 17.
Article
in En
| MEDLINE
| ID: mdl-29731414
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
RNA
/
Immunoglobulin Switch Region
/
Immunoglobulin Heavy Chains
/
Adenosine Triphosphatases
/
DEAD-box RNA Helicases
/
G-Quadruplexes
Limits:
Animals
Language:
En
Year:
2018
Type:
Article