SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network.
SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network.
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DOI：
10.1016/j.ebiom.2022.103861
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发表时间：
2022-03
期刊：
影响因子：
11.1
通讯作者：
Yu W
中科院分区：
文献类型：
--
作者：
Li W;Yang S;Xu P;Zhang D;Tong Y;Chen L;Jia B;Li A;Lian C;Ru D;Zhang B;Liu M;Chen C;Fu W;Yuan S;Gu C;Wang L;Li W;Liang Y;Yang Z;Ren X;Wang S;Zhang X;Song Y;Xie Y;Lu H;Xu J;Wang H;Yu W
自2019年底以来，SARS-CoV-2感染导致COVID-19并伴有多种临床表现。然而，SARS-CoV-2如何与宿主相互作用并产生多种症状的潜在机制在很大程度上尚未探索。生物信息学分析确定了SARS-CoV-2与人类基因组的序列相似性。将SARS-CoV-2全基因组中含有人同源序列（HIS）的不同片段克隆到慢病毒载体中。用实验室包装的慢病毒感染HEK 293 T、MRC 5和HUVEC，或用质粒或质粒转染HIS。定量RT-PCR和染色质免疫沉淀法分别检测基因表达和H3 K27 ac富集。紫外-可见光谱法评价了HIS与其靶位点之间的相互作用。酶联免疫吸附试验评价了COVID-19患者培养上清液和血浆中的透明质酸（HA）水平。在SARS-CoV-2基因组中发现了5个与人类基因组相同的短序列（24-27 nt）。这些RNA元件在灵长类动物中高度保守。预测含有HIS的基因组片段在计算机上形成类似于miRNA前体的发夹结构。HIS可能通过直接基因组相互作用发挥作用，导致宿主增强子的激活，以及相邻和远端基因的上调，包括细胞因子基因和透明质酸合酶2（HAS 2）。HIS 13 d和HIS 13 d介导的HIS降解降低HAS 2表达。严重的COVID-19患者显示淋巴细胞减少，D-二聚体和C-反应蛋白升高，以及血浆透明质酸升高。羟甲香豆素在体外抑制透明质酸的产生，因此可以进一步研究其作为预防COVID-19患者严重结局的治疗选择。SARS-CoV-2的HIS可以通过上调透明质酸促进COVID-19的进展，为治疗提供了新的靶点。国家重点研发计划（2018 YFC 1005004）、上海市科委基础研究重大专项（18 JC 1411101）、国家自然科学基金（31872814、32000505）。
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. 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. 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. HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. 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).
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影响因子：
3.7
作者：
Bernard, Hans-Ulrich
通讯作者：
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影响因子：
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作者：
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DOI：
10.1261/rna.078923.121
发表时间：
2021-11
期刊：
RNA (New York, N.Y.)
影响因子：
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