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  • The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers.

The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers.

Cell host & microbe (2019-09-13)
Lili Cao, Shengde Liu, Yunfei Li, Guang Yang, Yujie Luo, Siji Li, Hongqiang Du, Yingchi Zhao, Dandan Wang, Jingxuan Chen, Zeming Zhang, Mo Li, Songying Ouyang, Xiang Gao, Yujie Sun, Zekun Wang, Long Yang, Rongtuan Lin, Penghua Wang, Fuping You
RESUMO

Pathogen pattern recognition receptors (PRRs) trigger innate immune responses to invading pathogens. All known PRRs for viral RNA have extranuclear localization. However, for many viruses, replication generates dsRNA in the nucleus. Here, we show that the nuclear matrix protein SAFA (also known as HnRNPU) functions as a nuclear viral dsRNA sensor for both DNA and RNA viruses. Upon recognition of viral dsRNA, SAFA oligomerizes and activates the enhancers of antiviral genes, including IFNB1. Moreover, SAFA is required for the activation of super-enhancers, which direct vigorous immune gene transcription to establish the antiviral state. Myeloid-specific SAFA-deficient mice were more susceptible to lethal HSV-1 and VSV infection, with decreased type I IFNs. Thus, SAFA functions as a nuclear viral RNA sensor and trans-activator to bridge innate sensing with chromatin remodeling and potentiate robust antiviral responses.

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