Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.23.263327v1?rss=1 Authors: Shan, G., Zhi, C., Xiufeng, J., Fang, W., Yibo, X., Hao, Z., Chang, L., Jishou, R., Guangyou, D., Xin, L. Abstract: Background: Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the replication and transcription mechanisms of SARS-CoV-2 have been preliminarily revealed recently, their regulation is still unclear. Results: By reanalysis of public data, we proposed a negative feedback model to explain the regulation of replication and transcription of, but not limited to coronavirus (CoVs). The key step leading to new discoveries is that we identified the cleavage sites of nps15, an RNA uridylate-specific endoribonuclease. According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs) or genomic RNAs (gRNAs) by cleavage of transcription regulatory sequences in the body. The expression level of nsp15 determines the relative proportions of sgRNAs and gRNAs. The increase of nsp15 results in the decrease of itself to reach equilibrium between the replication and transcription of CoVs. Conclusions: The replication and transcription of CoVs are regulated by a negative feedback strategy. This is a basic mechanism to influence the persistence of CoVs in hosts. Our study indicates that nsp15 is an important and ideal target for drug development against CoVs. Copy rights belong to original authors. Visit the link for more info