Viral infection triggers induction of type I interferons (IFNs), which are critical mediators of innate antiviral immune response. Mediator of IRF3 activation (MITA, also called STING) is an adapter essential for virus-triggered IFN induction pathways. How post-translational modifications regulate the activity of MITA is not fully elucidated. In expression screens, we identified RING finger protein 26 (RNF26), an E3 ubiquitin ligase, could mediate polyubiquitination of MITA. Interestingly, RNF26 promoted K11-linked polyubiquitination of MITA at lysine 150, a residue also targeted by RNF5 for K48-linked polyubiquitination. Further experiments indicated that RNF26 protected MITA from RNF5-mediated K48-linked polyubiquitination and degradation that was required for quick and efficient type I IFN and proinflammatory cytokine induction after viral infection. On the other hand, RNF26 was required to limit excessive type I IFN response but not proinflammatory cytokine induction by promoting autophagic degradation of IRF3. Consistently, knockdown of RNF26 inhibited the expression of IFNB1 gene in various cells at the early phase and promoted it at the late phase of viral infection, respectively. Furthermore, knockdown of RNF26 inhibited viral replication, indicating that RNF26 antagonizes cellular antiviral response. Our findings thus suggest that RNF26 temporally regulates innate antiviral response by two distinct mechanisms.

These results suggest, for the first time, the genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women.

Coronavirus disease‐2019 (COVID‐19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID‐19, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS‐CoV. The pathological investigation of COVID‐19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS‐CoV‐2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell‐type‐specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single‐cell RNA‐seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS‐CoV‐2. Failed human hearts have a higher percentage of ACE2‐expressing cardiomyocytes, and SARS‐CoV‐2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS‐CoV‐2 infection. The SARS‐CoV‐2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS‐CoV‐2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.