85 : A novel role for the oligoadenylate synthetase-like protein in viral recognition and interferon induction

Abstract

One of the most important pattern-recognition receptors in terms of recognition of viral RNAs in the cytoplasm is the retinoic acid inducible gene I (RIG-I). Following viral infection, RIG-I predominantly recognizes short double-stranded RNAs (dsRNA) containing triphosphate at their 5′ end and triggers a distinct signal transduction pathway leading to induction of cytokines such as interferon (IFN) as well as other antiviral proteins. Activation of RIG-I is regulated at several levels by cellular proteins in order to both prevent undue activation of the innate immune response and to increase the efficiency of RIG-I-mediated signalling. In recent years, it has become clear that ubiquitination plays a key role in regulating RIG-I-mediated signalling and in order to become activated, RIG-I needs not only to bind viral RNA but also free unanchored K63-linked polyubiquitin chains. However, our collaborator Saumendra N. Sarkar from the University of Pittsburgh Cancer Institute, USA, has recently discovered that another IFN-stimulated protein can act as a substitute for polyubiquitin in activation of RIG-I. This protein is known as the oligoadenylate synthetase-like protein (OASL) and interacts with the RIG-I caspase recruitment domains (CARD) through its two C-terminal ubiquitin-like repeats. Furthermore, the C-terminal domain of RIG-I and the N-terminal domain of OASL, which both binds dsRNA, were shown to interact with each other. We aim to characterize the mechanism by which OASL induces RIG-I signalling and understand the functional consequences of dsRNA recognition by OASL and I will present recent work on this topic.