Circular RNA-MicroRNA-MRNA interaction predictions in SARS-CoV-2 infection.

Different types of noncoding RNAs like microRNAs (miRNAs) and circular RNAs (circRNAs) have been shown to take part in various cellular processes including post-transcriptional gene regulation during infection. MiRNAs are expressed by more than 200 organisms ranging from viruses to higher eukaryotes. Since miRNAs seem to be involved in host-pathogen interactions, many studies attempted to identify whether human miRNAs could target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNAs as an antiviral defence mechanism. In this work, a machine learning based miRNA analysis workflow was developed to predict differential expression patterns of human miRNAs during SARS-CoV-2 infection. In order to obtain the graphical representation of miRNA hairpins, 36 features were defined based on the secondary structures. Moreover, potential targeting interactions between human circRNAs and miRNAs as well as human miRNAs and viral mRNAs were investigated.

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

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.