Poster abstracts
Poster number 17 submitted by Janhavi Sahasrabudhe
The Myddosome and CBM signalosome interact with RNA
Janhavi R. Sahasrabudhe (Division of Immunobiology, Cincinnati Childrens Hospital Medical Center), Nandan S. Gokhale (Division of Immunobiology, Cincinnati Childrens Hospital Medical Center)
Abstract:
Innate immune signaling is crucial to our health as it defends against pathogens. This signaling is initiated by pattern recognition receptors (PRRs), including RIG-I like receptors (RLRs), Toll-like receptors (TLRs), or C-type lectin receptors (CLRs). Upon sensing pathogens, these PRRs activate NF-kB or interferon pathways, ultimately leading to production of proinflammatory cytokines and changes in cellular state aimed at defending the host. To produce the appropriate responses and avoid systemic inflammation, these pathways must be tightly regulated. These pathways depend on multiprotein signaling complexes (signalosomes), centered on oligomerized adaptor proteins. Signalosomes can be modulated by various actions, including subcellular localization, post-translational modifications and protein-protein interactions. Recent work from our lab has also shown that RNA-protein interactions play a role in regulating the antiviral MAVS signalosome. This led us to hypothesize that other innate immune signalosomes may also be modulated by RNA binding.
The goal of this project is to examine if two signalosomes, the myddosome required for TLR signaling, and the CARD9-BCL10-MALT1 (CBM) signalosome required for antfungal CLR signaling, can interact with RNA, and to discover the function of RNA association with these complexes in innate immunity. Using irCLIP RNase-treated sucrose gradient fractionation, we find that MyD88, the adaptor protein at the myddosome, interacts with RNA through specific domains. Further, MyD88 interactions with RNA alter crucial protein-protein interactions. Currently, we are examining the function of RNA-protein interactions at the myddosome. Similarly, we find that CARD9 and BCL10 also interact with RNA and we will seek to determine the function of RNA at the CBM signalosome.
Keywords: MyD88, CBM, RNA