B-lymphocytes are cells of the immune system responsible for the production of antibodies, and do so by employing hazardous mechanisms of somatic DNA mutation and DNA deletion-recombination with remarkable efficiency. Increasing evidence suggests a significant contribution of RNA-mediated processes in regulating antibody gene rearrangements, although only a few RNA-binding proteins (RBPs) have been implicated so far.

Our research focuses on the role of RNA helicases, an important class of RBPs involved in remodelling RNA secondary structure and ribonucleoprotein complexes. We have found the RNA helicase DDX1 to be required for Class Switch Recombination, to modulate R-loop (RNA:DNA hybrid) and G-quadruplex (G4) structures present in CSR-induced long non-coding RNAs (Ribeiro de Almeida, 2018). These findings support a role for G4 RNA and DDX1 in targeting the CSR-catalysing enzyme activation-induced cytidine deaminase (AID) to the immunoglobulin heavy-chain (IgH) locus and initiate DNA mutation.

At present we are working on understanding how DDX1 and other RNA helicases are involved in regulating AID targeting specificity during B-lymphocyte immune responses. These studies will elucidate the fundamental molecular mechanisms underlying the ability of B-lymphocytes to mount effective antibody responses against pathogens, while maintaining genome stability and cellular homeostasis.