Abstract
Competing endogenous RNAs (ceRNA) play a crucial role in cell functions. Computational methods that provide large-scale analysis of the interactions between miRNAs and their competitive targets can contribute to the understanding of ceRNA regulations and critical regulatory functions. Recent reports showed that viral RNAs can compete with host RNAs against host miRNAs. Regarding SARS-CoV-2 RNA, no comprehensive study had been reported about its competition with cellular ceRNAs. In this study, for the first time, we used the ceRNAnetsim package to assess ceRNA network effects per individual cell and competitive behavior of SARS-CoV-2 RNA in the infected cells using single-cell sequencing data. Our computations identified 195 genes and 29 miRNAs which vary in competitive behavior specifically in presence of SARS-CoV-2 RNA. We also investigated 18 genes that are affected by genes that lost perturbation ability in presence of SARS-CoV-2 RNA in the human miRNA:ceRNA network. These transcripts have associations with COVID-19-related symptoms as well as many dysfunctions such as metabolic diseases, carcinomas, heart failure. Our results showed that the effects of the SARS-CoV-2 genome on host ceRNA interactions and consequent dysfunctions can be explained by competition among various miRNA targets. Our perturbation ability perspective has the potential to reveal yet to be discovered SARS-CoV-2 induced effects invisible to conventional approaches.
Highlights
More than 4.5 million people have died and millions were infected worldwide as of writing this manuscript due to COVID-19 caused by severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (WHO, 2021)
For Competing endogenous RNAs (ceRNA) networks containing SARS-CoV RNA, existing networks were extended with miRNAs potentially target viral RNAs (Khan et al, 2020; Chow & Salmena, 2020; Demirci & Adan, 2020; Fulzele et al, 2020). 129 miRNAs targeted SARS-CoV-1 RNA, 39 of which have already been in the ceRNA network, so the network was extended by 90 miRNAs
For SARS-CoV-2, 51 miRNAs targeted SARS-CoV-1 RNA, 14 of which have already been in the ceRNA network, so the network was extended by 37 miRNAs (Fig. S1)
Summary
More than 4.5 million people have died and millions were infected worldwide as of writing this manuscript due to COVID-19 caused by severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (WHO, 2021). Understanding the infection mechanism and causes of dysfunctions in infected cells in order to develop therapeutic strategies was of utmost importance in midst of the global pandemic. SARS-CoV-2 enters the cell through the binding of its structural protein S with the extracellular membrane proteins of the host cell (ACE2 and TMPRSS2). After the release of viral genomic RNA (ss+RNA) in the cell, the microenvironment is established for viral replication by expression of non-structural proteins and biogenesis of viral replication organelles (V’kovski et al, 2020; de Wilde et al, 2017). Effect of SARS-CoV-2 infection on host competing endogenous RNA and miRNA network.
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