| SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network | |
Li, Wei; Yang, Shuai; Xu, Peng ; Zhang, Dapeng; Tong, Ying; Chen, Lu; Jia, Ben; Li, Ang; Lian, Cheng; Ru, Daoping; Zhang, Baolong; Liu, Mengxing; Chen, Cancan; Fu, Weihui; Yuan, Songhua; Gu, Chenjian; Wang, Lu; Li, Wenxuan; Liang, Ying; Yang, Zhicong; Ren, Xiaoguang; Wang, Shaoxuan; Zhang, Xiaoyan; Song, Yuanlin; Xie, Youhua; Lu, Hongzhou; Xu, Jianqing; Wang, Hailin; Yu, Wenqiang
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| 2022-02 | |
| Source Publication | EBIOMEDICINE
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| ISSN | 2352-3964 |
| Volume | 76Issue:0Pages:103861 |
| Abstract | Background Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical man-ifestations. 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 lenti-viral 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 geno-mic 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). Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Department | 环境化学与生态毒理学国家重点实验室 ; 环境化学与生态毒理学国家重点实验室 |
| Keyword | VIRUS INFECTION TRANSCRIPTION MITOCHONDRIA SPECIFICITY MICRORNAS GENES ACID LUNG |
| Document Type | 期刊论文 |
| Identifier | https://ir.rcees.ac.cn/handle/311016/47613 |
| Collection | 环境化学与生态毒理学国家重点实验室 |
| Affiliation | 1.Fudan Univ, Shanghai Med Coll, Lab RNA Epigenet, Huashan Hosp,Canc Metastasis Inst,Inst Biomed Sci, Shanghai 200032, Peoples R China 2.Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Huashan Hosp,Canc Metastasis Inst, Shanghai 200032, Peoples R China 3.Fudan Univ, Shanghai Med Coll, Dept Gen Surg, Huashan Hosp,Canc Metastasis Inst, Shanghai 200032, Peoples R China 4.Shanghai Key Lab Med Epigenet, Shanghai 200032, Peoples R China 5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 10 |
| Recommended Citation GB/T 7714 | Li, Wei,Yang, Shuai,Xu, Peng,et al. SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network[J]. EBIOMEDICINE,2022,76(0):103861. |
| APA | Li, Wei.,Yang, Shuai.,Xu, Peng.,Zhang, Dapeng.,Tong, Ying.,...&Yu, Wenqiang.(2022).SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network.EBIOMEDICINE,76(0),103861. |
| MLA | Li, Wei,et al."SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network".EBIOMEDICINE 76.0(2022):103861. |
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