On July 17th 2018, Nature Communications published online a research article entitled “Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop” from Prof. Xiaojian Wang’s and Prof. Jihong Sun’s groups. This study reveals that the serine/threonine kinase NDR1 functions as a transcriptional regulator, enhancing antiviral innate immunity by upregulating STAT1 translation via inhibiting miR146a transcription.

Specifically, the researchers found that nuclear Dbf2-related kinase 1 (NDR1) potentiates the antiviral immune response in a kinase-independent manner. NDR1 deficiency renders mice more susceptible to viral and bacterial infection. Mechanistically, NDR1 enhances STAT1 translation by directly binding to the intergenic region of miR146a, thereby inhibiting miR146a expression and liberating STAT1 from miR146a-mediated translational inhibition. Furthermore, STAT1 binds to the miR146a promoter to repress its expression, which forms a mutual negative feedback loop between miR146a and STAT1. More importantly, virus infection downregulates NDR1 expression to imbalance the mutual inhibition between miR146a and STAT1, which results in deceased STAT1 expression and impaired ISGs expression to benefit virus to escape from the innate immune response.

These findings not only provide insight into the novel mechanism of mutual inhibition between STAT1 and miR146a, but also provide a novel transcription regulation mechanism that allows NDR1 to act as an antiviral molecule. The study was completed by the postdoctoral research fellow Zhiyong Liu and a Ph.D. student Qiang Qin. This work was supported by the National Foundation of Natural Science of China and National Basic Research Program of China (973).