REC8 meiotic recombination protein (REC8) is a member of structural maintenance of chromosome (SMC) protein partners, which play an important role in meiosis, anti-tumor, and sperm formation. As the adapter proteins of RLR signaling and cGAS-DNA signaling, the activity and stability of MAVS (also known as VISA, Cardif and IPS-1) and STING (also known as MITA) are critical for innate immunity. Here, we report that REC8 interacts with MAVS and STING, and inhibits their ubiquitination and subsequent degradation, thereby promoting innate antiviral signaling. REC8 is upregulated through the JAK-STAT signaling pathway under viral infection. Knockdown of REC8 impair the innate immune responses against VSV (Vesicular Stomatitis Virus), NDV (Newcastle disease virus) and HSV (herpes simplex virus). Mechanistically, under the infection of viruses, the SUMOylated REC8 is transferred from the nucleus to the cytoplasm and then interacts with MAVS and STING to inhibit their K48-linked ubiquitination triggered by RNF5. Moreover, REC8 promotes the recruitment of TBK1 to MAVS and STING. Thus, REC8 functions as a positive modulator of innate immunity. Our work highlights a previously undocumented role of meiosis-associated protein REC8 in regulating innate immunity. IMPORTANCE The innate immune response is crucial for the host to resist the invasion of viruses and other pathogens. STING and MAVS play a critical role in the innate immune response to DNA and RNA viral infection, respectively. In this study, REC8 promotes the innate immune response by targeting STING and MAVS. Notably, REC8 interacts with MAVS and STING in the cytoplasm and inhibits K48-linked ubiquitination of MAVS and STING triggered by RNF5, stabilizing MAVS and STING protein to promote innate immunity and gradually inhibiting viral infection. Our study provides a new insight for the study of antiviral innate immune.

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Callicarpa kwangtungenis (C. Kw), C. macroph ylla (C. Ma), C. nudiflora (C. Nu), C. formosana (C. Fo), and C. kochiana (C. Ko) were medicinal plant resource in China. The aim of this study is to fully identify the chemical components, explore the similarities and differences, as well as evaluate the anti-hyperuricemia effects of these five Callicarpa leaves extracts. The UPLC/Q-TOF-MS analysis was performed and 151 compounds were identified. PCA suggested that there exist large metabolite differences between these five callicarpa species extracts. Meanwhile, metabolic profiles of C. Nu, C. Ko and C. Kw leaves differ significantly from the other two callicarpa species, while C. Fo and C. Ma share similar chemical constituents. OPLS-DA highlight with an S-plot indicated that there are 14 robust known chemical markers enabling the differentiation between these five Callicarpa plants. What is more, C. Ma, C. Nu, and C. Fo leaves extracts treatment effectively reversed the body weight loss, uric acid and creatinine content, hepatic XOD activity, kidney, liver, and ankle tissues injury and inflammation induced by potassium oxonate in hyperuricemia mice. While Ko and C. Kw leaves extracts treatment showed less improvement in hyperuricemia mice. This study supplied new therapeutic medicines for treating hyperuricemia, provided a new direction for exploitation of Callicarpa plants resources.

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