STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection

文献类型： 外文期刊

第一作者： Ding, Siyuan

作者： Ding, Siyuan;Diep, Jonathan;Feng, Ningguo;Ren, Lili;Li, Bin;Ooi, Yaw Shin;Yasukawa, Linda L.;Carette, Jan E.;Greenberg, Harry B.;Ding, Siyuan;Feng, Ningguo;Ren, Lili;Yasukawa, Linda L.;Greenberg, Harry B.;Ding, Siyuan;Feng, Ningguo;Ren, Lili;Brulois, Kevin F.;Yasukawa, Linda L.;Greenberg, Harry B.;Ren, Lili;Li, Bin;Wang, Xin;Brulois, Kevin F.;Li, Xingnan;Kuo, Calvin J.;Solomon, David A.;Wang, Xin

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：14.919； 五年影响因子：15.805 ）

ISSN： 2041-1723

年卷期： 2018 年 9 卷

页码：

收录情况： SCI

摘要： Cohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids. Mechanistically, STAG2 deficiency results in spontaneous genomic DNA damage and robust interferon (IFN) expression via the cGAS-STING cytosolic DNA-sensing pathway. The resultant activation of JAK-STAT signaling and IFN-stimulated gene (ISG) expression broadly protects against virus infections, including RVs. Our work highlights a previously undocumented role of the cohesin complex in regulating IFN homeostasis and identifies new therapeutic avenues for manipulating the innate immunity.

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