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. 2022 Apr 8:9:866072.
doi: 10.3389/fmolb.2022.866072. eCollection 2022.

Prediction of Site Directed miRNAs as Key Players of Transcriptional Regulators Against Influenza C Virus Infection Through Computational Approaches

Mubashir Hassan  1   2 , Muhammad Shahzad Iqbal  3 , Sawaira Naqvi  1 , Hany Alashwal  4 , Ahmed A Moustafa  5   6 , Andrzej Kloczkowski  2   7
Affiliations

Prediction of Site Directed miRNAs as Key Players of Transcriptional Regulators Against Influenza C Virus Infection Through Computational Approaches

Mubashir Hassan et al. Front Mol Biosci. .

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene expression, cell differentiation, and immunity against viral infections. In this study, we have used the computational tools, RNA22, RNAhybrid, and miRanda, to predict the microRNA-mRNA binding sites to find the putative microRNAs playing role in the host response to influenza C virus infection. This computational research screened the following four miRNAs: hsa-mir-3155a, hsa-mir-6796-5p, hsa-mir-3194-3p and hsa-mir-4673, which were further investigated for binding site prediction to the influenza C genome. Moreover, multiple sites in protein-coding region (HEF, CM2, M1-M2, NP, NS1- NS2, NSF, P3, PB1 and PB2) were predicted by RNA22, RNAhybrid and miRanda. Furthermore, 3D structures of all miRNAs and HEF were predicted and checked for their binding potential through molecular docking analysis. The comparative results showed that among all proteins, HEF is higher in prevalence throughout the analysis as a potential (human-derived) microRNAs target. The target-site conservation results showed that core nucleotide sequence in three different strains is responsible for potential miRNA binding to different viral strains. Further steps to use these microRNAs may lead to new therapeutic insights on fighting influenza virus infection.

Keywords: HEF; RNAComposer; RStudio; influenza C virus; miRNAs; mirbase; target site prediction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of designed research work.
FIGURE 2
FIGURE 2
Influenza C virus genome. Prediction of new target-sites for miRNAs in influenza C virus.
FIGURE 3
FIGURE 3
Target sites for miRNAs binding to influenza C virus genome predicted by RNA22 algorithm. The color dots represent binding to genes coding the relevant proteins. The gray dots labeled as NA which indicate non-applicable.
FIGURE 4
FIGURE 4
Target sites of miRNAs in genome of influenza C virus predicted by miRanda algorithm. The color key represents the respective genes/proteins in the graph. The gray dots labeled as NA which indicate non-applicable.
FIGURE 5
FIGURE 5
Target sites of human miRNAs in genome of influenza C virus predicted by RNAhybrid server. The color key represents the respective genes in the graph. The gray dots labeled as NA which indicate non-applicable.
FIGURE 6
FIGURE 6
The Venn diagram of miRNAs predicted to bind to influenza C virus genomein by all three different tools: RNAhybrid, RNA22, and miRanda. The intersection graph showed four common miRNAs: hsa-mir-3155a, hsa-mir-6796-5p, hsa-mir-3194-3p and hsa-mir-4673, respectively.
FIGURE 7
FIGURE 7
(A,B) The predicted 3D structures of premature and mature has_mir_4673 and has_mir_3194_3p miRNAs, respectively.
FIGURE 8
FIGURE 8
(A,B) 3D structures of premature and mature miRNAs hsa_mir_6796-5p and has_mir_3155a, miRNAs respectively.
FIGURE 9
FIGURE 9
Target-site conservation pattern in different influenza strains. The target sites are highlighted in blue, and bars show the level of conservation at specific sites. Involvement of predicted proteins in influenza c virus.
FIGURE 10
FIGURE 10
Bar chart of predicted proteins.
FIGURE 11
FIGURE 11
Docking energy values of top 10 best complexes.
FIGURE 12
FIGURE 12
Docking complex of hsa-miRNA-3155a.
FIGURE 13
FIGURE 13
Mechanistic pathway of miRNA formation from premature miRNA.
FIGURE 14
FIGURE 14
Mechanistic pathway of miRNAs involvement in the immune response.
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