Science 365, eaav0758 (2019)

Recognition of DNA viruses within the nucleus triggers the production of type I interferon. In Science, Wang et al. report that the host ribonucleoprotein hnRNPA2B1 serves as a nuclear sensor of viral DNA. Nuclear hnRNPA2B1 dimerizes after recognition of viral DNA, which promotes demethylation of hnRNPA2B1 by the arginine demethylase JMJD6 and translocation of hnRNPA2B1 to the cytosol; there, it associates with the adaptor STING and the kinases Src and TBK1 to activate the transcription factor IRF3, which ensures expression of type I interferon. Additionally, hnRNPA2B1 enhances anti-viral innate immunity by promoting N6-methyladenosine modification of mRNAs encoding STING, cGAS and IFI16 to enhance their export from the nucleus and translation and thus boosts the abundance of these cytosolic anti-viral sensors at later time points after the recognition of DNA viruses. Thus, the recognition of viral DNA by nuclear hnRNPA2B1 coordinates the cellular anti-viral immune responses.