A potential role for SARS-CoV-2 small viral RNAs in targeting host microRNAs and modulating gene expression.
A potential role for SARS-CoV-2 small viral RNAs in targeting host microRNAs and modulating gene expression.
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DOI：
10.1038/s41598-022-26135-9
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发表时间：
2022-12-15
影响因子：
4.6
通讯作者：
Sanford, Jeremy R.
中科院分区：
文献类型：
--
作者：
Neeb, Zachary T.;Ritter, Alexander J.;Chauhan, Lokendra V.;Katzman, Sol;Lipkin, W. Ian;Mishra, Nischay;Sanford, Jeremy R.
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)会导致人类患上冠状病毒病(新冠肺炎)，症状从轻到重，包括死亡。围绕病毒感染对宿主RNA机制的影响的分子机制仍然没有得到很好的描述。我们使用比较转录组学方法研究了SARS-CoV-2感染对人肺上皮细胞系(CALU-3)和非洲绿猴肾细胞系(Vero-E6)宿主mRNA和sRNA表达机制的影响。感染后，我们观察到宿主基因表达的全球变化和数十个宿主miRNAs的差异表达，其中许多与病毒感染和免疫反应有关。此外，我们还发现了100多个SARS-CoV-2来源的小病毒RNA(SvRNAs)的扩展版图，预计它们将与差异表达的宿主mRNAs和miRNAs相互作用。SvRNA来自病毒基因组的不同区域，序列签名表明它们是由非规范的生物发生途径产生的。在CALU-3细胞中发现的67个svRNAs中，有52个被预测与差异表达的miRNAs相互作用，许多svRNAs具有多个靶点。因此，我们推测这些svRNAs可能通过调节转录后基因调控在SARS-CoV-2的传播中发挥作用，而拮抗它们的方法可能具有治疗价值。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19) in humans, with symptoms ranging from mild to severe, including fatality. The molecular mechanisms surrounding the effects of viral infection on the host RNA machinery remain poorly characterized. We used a comparative transcriptomics approach to investigate the effects of SARS-CoV-2 infection on the host mRNA and sRNA expression machinery in a human lung epithelial cell line (Calu-3) and an African green monkey kidney cell line (Vero-E6). Upon infection, we observed global changes in host gene expression and differential expression of dozens of host miRNAs, many with known links to viral infection and immune response. Additionally, we discovered an expanded landscape of more than a hundred SARS-CoV-2-derived small viral RNAs (svRNAs) predicted to interact with differentially expressed host mRNAs and miRNAs. svRNAs are derived from distinct regions of the viral genome and sequence signatures suggest they are produced by a non-canonical biogenesis pathway. 52 of the 67 svRNAs identified in Calu-3 cells are predicted to interact with differentially expressed miRNAs, with many svRNAs having multiple targets. Accordingly, we speculate that these svRNAs may play a role in SARS-CoV-2 propagation by modulating post-transcriptional gene regulation, and that methods for antagonizing them may have therapeutic value.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
16.6
作者：
Gassen NC;Papies J;Bajaj T;Emanuel J;Dethloff F;Chua RL;Trimpert J;Heinemann N;Niemeyer C;Weege F;Hönzke K;Aschman T;Heinz DE;Weckmann K;Ebert T;Zellner A;Lennarz M;Wyler E;Schroeder S;Richter A;Niemeyer D;Hoffmann K;Meyer TF;Heppner FL;Corman VM;Landthaler M;Hocke AC;Morkel M;Osterrieder N;Conrad C;Eils R;Radbruch H;Giavalisco P;Drosten C;Müller MA
通讯作者：
Müller MA
DOI：
10.1126/science.1187197
发表时间：
2010-06-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cazalla D;Yario T;Steitz JA
通讯作者：
Steitz JA
影响因子：
8.8
作者：
Furrer DI;Swart EC;Kraft MF;Sandoval PY;Nowacki M
通讯作者：
Nowacki M