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

• Applicant: Professorin Dr. Anne Krug
• Subject Area: Cell Biology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218723433

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.

• DFG Programme: Research Grants