Regulation of RIG-I signaling by a a novel interferon-inducible short form of RIG-I

点击翻译按钮获取中文摘要

Retinoic acid inducible gene I (RIG-I) belongs to a family of cytosolic RNA helicases, which recognizes viral RNA ligands and is critical for the induction of innate antiviral responses especially type I Interferon (IFN) production. RIG-I activation and downstream signaling is tightly regulated to avoid excessive innate immune responses, which might have deleterious effects on the host, while ensuring sufficient control of viral infection. We have identified a type I IFN inducible novel short form of human RIG-I with negative regulatory function by immunoprecipitation and mass spectrometry analysis. This short form of RIG-I is induced by type I IFN and by RIG-I activation at late time points and might therefore be a critical molecule for shutting off the RIG-I triggered type I IFN response at the right time point after viral infection. The aims of this proposal are therefore: i) to elucidate the origin of RIG-I short form which might be generated by proteolytic degradation or translation of an alternative open reading frame, ii) to study the expression of RIG-I short form in human primary cells and in the mouse in vivo after exposure to RIG-I ligand or during viral infection, and iii) to investigate how this novel short form of RIG-I exerts its negative regulatory function on RIG-I activation and signaling.