The Role of RNA Helicase RHAU in Immunoglobulin Class Switch Recombination

B cells alter the expression of immunoglobulin isotypes through a process known as class switch recombination (CSR). In these cells, activation induced cytidine deaminase (AID) binds Gquadruplex (G4) switch transcripts, which serve as guide RNAs to target AID to the immunoglobulin heavy chain switch (S) regions in the DNA for CSR. Sequence alignment revealed homology between the AID G4 binding domain and the RNA helicase associated with AU-rich element (RHAU) specific motif (RSM), which allows RHAU binding to G4 RNAs and subsequent unwinding of G4 RNA into single-stranded transcripts. We hypothesize that RHAU functions in CSR by binding G4 S transcripts and resolving them into linear transcripts which base pair with the immunoglobulin heavy chain S region DNA to localize AID specifically to the recombining S regions. To test this hypothesis, we conditionally deleted floxed Rhau alleles in mouse B cells using a CD23-cre transgene. RhauD/D B cells show decreased in vitro CSR to IgG1 and RhauD/D mice display decreased IgG1, IgA, and IgG3 titers, suggesting that RHAU regulates CSR