LUBAC is required for RIG-I sensing of RNA viruses

Teague, H. C.; Lefevre, C.; Rieser, E.; de Miguel, D.; Patricio, D.; Oliveira, M.; Mansur, D. S.; Irigoyen, N.; Walczak, H.; Ferguson, B. J.

doi:10.1101/2022.02.24.481814

bioRxiv · 10.1101/2022.02.24.481814

LUBAC is required for RIG-I sensing of RNA viruses

Teague, H. C.·Lefevre, C.·Rieser, E.·de Miguel, D.·Patricio, D.·Oliveira, M.·Mansur, D. S.·Irigoyen, N.·Walczak, H.·Ferguson, B. J.

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Abstract

The ability of cells to mount an interferon response to virus infections depends on intracellular nucleic acid sensing pattern recognition receptors (PRRs). RIG-I is an intracellular PRR that binds short double stranded viral RNAs to trigger MAVS-dependent signalling. The RIG-I/MAVS signalling complex requires the coordinated activity of multiple kinases and E3 ubiquitin ligases to activate the transcription factors that drive type I and type III interferon production from infected cells. The linear ubiquitin chain assembly complex (LUBAC) regulates the activity of multiple receptor signalling pathways in both ligase-dependent and -independent ways. Here, we show that the three proteins that constitute LUBAC have separate functions in regulating RIG-I signalling. Both HOIP, the E3 ligase capable of generating M1-ubiquitin chains, and LUBAC accessory protein HOIL-1 are required for viral RNA sensing by RIG-I. The third LUBAC component, SHARPIN, is not required for RIG-I signalling. These data cement the role of LUBAC as a positive regulator of RIG-I signalling and as an important component of antiviral innate immune responses.

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Teague, H. C., Lefevre, C., Rieser, E., de Miguel, D., Patricio, D., Oliveira, M., Mansur, D. S., Irigoyen, N., Walczak, H., Ferguson, B. J.. 2022-02-24. LUBAC is required for RIG-I sensing of RNA viruses. https://doi.org/10.1101/2022.02.24.481814

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