Cited by 190MicroRNA in disease regulationSARS-CoV-2 and COVID-19 ResearchRNA regulation and disease

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Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

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Saçar Demirci, Müşerref Duygu, Adan, Aysun·2020·PeerJ

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Abstract

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs, there are examples of miRNA like sequences from RNA viruses with regulatory functions. In the case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with viral replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA-based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Overall, 950 hairpin structured sequences were extracted from the virus genome and based on the prediction results, 29 of them could be precursor miRNAs. Targeting analysis showed that 30 viral mature miRNA-like sequences could target 1,367 different human genes. PANTHER gene function analysis results indicated that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription, metabolism, defense system and several signaling pathways such as Wnt and EGFR signalings. Protein class-based grouping of targeted human genes showed that host transcription might be one of the main targets of the virus since 96 genes involved in transcriptional processes were potential targets of predicted viral miRNAs. For instance, basal transcription machinery elements including several components of human mediator complex (MED1, MED9, MED12L, MED19), basal transcription factors such as TAF4, TAF5, TAF7L and site-specific transcription factors such as STAT1 were found to be targeted. In addition, many known human miRNAs appeared to be able to target viral genes involved in viral life cycle such as S, M, N, E proteins and ORF1ab, ORF3a, ORF8, ORF7a and ORF10. Considering the fact that miRNA-based therapies have been paid attention, based on the findings of this study, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections could create new opportunities for the development and improvement of new therapeutics.

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Figure 1 Box-plots for comparison of general features of human pre-miRNAs and virus pre-miRNAs from miRBase and SARS-CoV-2 hairpins. (A) Hairpin lengths. (B) Minimum free energy scores obtained from RNAfold (Hofacker, 2003). SARS-CoV-2 refers to all 950 hairpins extracted from the virus genome while SARS-CoV-2* indicates 29 selected hairpins.CC BY · PubMed Central

Figure 2 Bar-chart for the protein classes of human genes that could be targeted by viral miRNAs. Protein classes of genes were obtained from Panther. X-axis shows the number of genes with respected classes.CC BY · PubMed Central

Figure 3 Bar-chart for the pathways of human genes that could be targeted by viral miRNAs. Graph is limited to the pathways that have at least 10 genes. Pathways of genes were obtained from Panther. Y-axis shows the number of genes with respected pathways. Chart and legend are sorted from maximum to minimum (left to right and top to bottom, respectively).CC BY · PubMed Central

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Authors: Saçar Demirci, M. D., & Adan, A.
Affiliations: Bioinformatics, Abdullah Gul University, Kayseri, Turkey
Abdullah Gül University (TR)
ORCID: Saçar Demirci, Müşerref Duygu
Adan, Aysun
Venue: PeerJ
Publisher: PeerJ
Published: 2020-06-05
Volume: 8
Pages: e9369
ISSN: 2167-8359 (ISSN-L)
DOI: 10.7717/peerj.9369
PMC: PMC7278893
OpenAlex: W3033005856
Cited by: 190
References: 58
Citations by year: 2026: 4 · 2025: 6 · 2024: 18 · 2023: 25 · 2022: 44 · 2021: 67 · 2020: 26
FWCI: 13.88
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PeerJ (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: SARS-CoV-2, microRNA, miRNA target prediction, host-virus interaction, Mediator complex, STAT1, viral proteins, miRNA-based therapy, post-transcriptional regulation

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Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

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