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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染细胞中长链非编码RNA表达改变及其受信号转导和转录激活因子1(STAT1)、信号转导和转录激活因子3(STAT3)以及干扰素调节因子调控的分析

analysis of altered expression of long non-coding RNA in SARS-CoV-2 infected cells and their possible regulation by STAT1, STAT3 and interferon regulatory factors.

作者信息

Laha Sayantan, Saha Chinmay, Dutta Susmita, Basu Madhurima, Chatterjee Raghunath, Ghosh Sujoy, Bhattacharyya Nitai P

机构信息

Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata 700108, India.

Department of Genome Science, School of Interdisciplinary Studies, University of Kalyani, Nadia 741235, India.

出版信息

Heliyon. 2021 Mar;7(3):e06395. doi: 10.1016/j.heliyon.2021.e06395. Epub 2021 Feb 27.

Abstract

Altered expression of long noncoding RNA (lncRNA), longer than 200 nucleotides without potential for coding protein, has been observed in diverse human diseases including viral diseases. It is largely unknown whether lncRNA would deregulate in SARS-CoV-2 infection, causing ongoing pandemic COVID-19. To identify, if lncRNA was deregulated in SARS-CoV-2 infected cells, we analyzed in silico the data in GSE147507. It was revealed that expression of 20 lncRNA like MALAT1, NEAT1 was increased and 4 lncRNA like PART1, TP53TG1 was decreased in at least two independent cell lines infected with SARS-CoV-2. Expression of NEAT1 was also increased in lungs tissue of COVID-19 patients. The deregulated lncRNA could interact with more than 2800 genes/proteins and 422 microRNAs as revealed from the database that catalogs experimentally determined interactions. Analysis with the interacting gene/protein partners of deregulated lncRNAs revealed that these genes/proteins were associated with many pathways related to viral infection, inflammation and immune functions. To find out whether these lncRNAs could be regulated by STATs and interferon regulatory factors (IRFs), we used ChIPBase v2.0 that catalogs experimentally determined binding from ChIP-seq data. It was revealed that any one of the transcription factors IRF1, IRF4, STAT1, STAT3 and STAT5A had experimentally determined binding at regions within -5kb to +1kb of the deregulated lncRNAs in at least 2 independent cell lines/conditions. Our analysis revealed that several lncRNAs could be regulated by IRF1, IRF4 STAT1 and STAT3 in response to SARS-CoV-2 infection and lncRNAs might be involved in antiviral response. However, these in silico observations are necessary to be validated experimentally.

摘要

在包括病毒性疾病在内的多种人类疾病中,人们观察到长度超过200个核苷酸且无编码蛋白质潜力的长链非编码RNA(lncRNA)表达发生了改变。在导致当前大流行的新型冠状病毒肺炎(COVID-19)中,lncRNA是否失调很大程度上尚不清楚。为了确定lncRNA在感染新型冠状病毒2(SARS-CoV-2)的细胞中是否失调,我们对GSE147507中的数据进行了计算机分析。结果显示,在至少两个独立的感染SARS-CoV-2的细胞系中,如MALAT1、NEAT1等20种lncRNA的表达增加,而如PART1、TP53TG1等4种lncRNA的表达减少。在COVID-19患者的肺组织中,NEAT1的表达也增加。从记录实验确定相互作用的数据库中可以看出,失调的lncRNA可以与超过2800个基因/蛋白质和422个微小RNA相互作用。对失调lncRNA的相互作用基因/蛋白质伙伴的分析表明,这些基因/蛋白质与许多与病毒感染、炎症和免疫功能相关的途径有关。为了弄清楚这些lncRNA是否受信号转导和转录激活因子(STATs)和干扰素调节因子(IRFs)调控,我们使用了ChIPBase v2.0,该数据库记录了来自ChIP-seq数据的实验确定的结合情况。结果显示,在至少2个独立细胞系/条件下,转录因子IRF1、IRF4、STAT1、STAT3和STAT5A中的任何一个在失调lncRNA的-5kb至+1kb区域内都有实验确定的结合。我们的分析表明,几种lncRNA在SARS-CoV-2感染时可能受IRF1、IRF4、STAT1和STAT3调控,并且lncRNA可能参与抗病毒反应。然而,这些计算机分析结果需要通过实验进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a8b/7937986/494622eac90c/gr1.jpg

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