RNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I

RIG-I like helicases (RLHs) and cGAS are crucial cytosolic sensors of viral RNA and DNA, respectively, and induce type I IFNs via TBK1/IKKε. hnRNPM was described to possess antimicrobial activities. Here, we show that hnRNPM promotes IRF3 phosphorylation and type I IFN induction downstream of cGAS and RIG-I in THP-1 cells and primary human fibroblasts. Interactome analysis revealed that hnRNPM forms a multiprotein complex with ELAVL1, TBK1, IKKε, IKKβ, and NF-κB p65. hnRNPM, ELAVL1, and TBK1 predominantly interacted in the cytosol. To our knowledge, hnRNPM and ELAVL1 represent the first non-redundant signaling components merging the cGAS-STING and RIG-I–MAVS pathways. Therefore, our findings may have implications for host defense and auto-inflammatory diseases. 3'-mRNA expression profiles of THP-1 dual wildtype (WT) and ELAVL1 knockout (KO) cells 6 h after stimulation of the interferon-α/β receptor (IFNAR) with 1000 U/ml interferon-α (IFNα)