The DEAH-box Helicase RHAU Regulates Immunoglobulin Class Switch Recombination.

---

Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B732
Abstract ID: 5240

Presenting Author:
Sadman Shawraz , Research Technician at City Col., CUNY

Abstract:

B cells produce alternative immunoglobulin isotypes (IgG, IgA, IgE) through class switch recombination (CSR). Initiation of CSR requires AID-mediated deamination of switch (S) regions in the immunoglobulin heavy chain (IgH) locus. G-quadruplex(G4)-forming S region RNAs bind to AID and localize AID to sequence-specific S region DNA sequences; however, the molecular mechanism that transfers AID binding from G4-RNA to DNA remains uncharacterized. We hypothesize that helicases disrupt G4-RNA to permit the base-pairing of the S transcript to the complementary DNA sequence in the IgH locus during CSR. We identified the DEAH-box family RNA Helicase associated with AU-rich element (RHAU), as an S transcript binding protein. We genetically deleted a floxed Rhau allele (Rhau^F) in mouse B cells expressing Cre recombinase under the control of the CD23 promoter (CD23-Cre) to produce a deleted Rhau allele (Rhau^Δ). Rhau^Δ/Δ mice produced less serum IgG1, IgG2b, IgG2c, and IgA but comparable IgM and IgG3 as compared to wild-type, CD23-cre⁺, and Rhau^F/F mice. In vitro stimulated Rhau^Δ/Δ B cells show decreased IgG1 and IgA CSR that correlates with reduced γ1- and ɑ germline transcription (GLT), respectively, as compared to the control genotypes. Surprisingly, IgG3 CSR and γ3-GLT increased. These data suggest that RHAU regulates GLT during CSR. Whether the altered GLT changes S transcript levels and thus AID localization and deamination remains to be determined.