EBioMedicine (Feb 2022)
SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network
- Wei Li,
- Shuai Yang,
- Peng Xu,
- Dapeng Zhang,
- Ying Tong,
- Lu Chen,
- Ben Jia,
- Ang Li,
- Cheng Lian,
- Daoping Ru,
- Baolong Zhang,
- Mengxing Liu,
- Cancan Chen,
- Weihui Fu,
- Songhua Yuan,
- Chenjian Gu,
- Lu Wang,
- Wenxuan Li,
- Ying Liang,
- Zhicong Yang,
- Xiaoguang Ren,
- Shaoxuan Wang,
- Xiaoyan Zhang,
- Yuanlin Song,
- Youhua Xie,
- Hongzhou Lu,
- Jianqing Xu,
- Hailin Wang,
- Wenqiang Yu
Affiliations
- Wei Li
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Shuai Yang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Peng Xu
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Dapeng Zhang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- Ying Tong
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Lu Chen
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Ben Jia
- Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, China
- Ang Li
- Institute of Clinical Science & Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
- Cheng Lian
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Daoping Ru
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Baolong Zhang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Mengxing Liu
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Cancan Chen
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Weihui Fu
- Institute of Clinical Science & Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
- Songhua Yuan
- Institute of Clinical Science & Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
- Chenjian Gu
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Lu Wang
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Wenxuan Li
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Ying Liang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Zhicong Yang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Xiaoguang Ren
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Shaoxuan Wang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China
- Xiaoyan Zhang
- Institute of Clinical Science & Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
- Yuanlin Song
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Youhua Xie
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Hongzhou Lu
- Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
- Jianqing Xu
- Institute of Clinical Science & Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; Corresponding authors.
- Hailin Wang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Corresponding authors.
- Wenqiang Yu
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Epigenetics, Shanghai 200032, China; Corresponding author at: Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China.
- Journal volume & issue
-
Vol. 76
p. 103861
Abstract
Summary: Background: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. Methods: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. Findings: Five short sequences (24–27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. Interpretation: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. Funding: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).
