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. 2020 Nov 4:11:605054.
doi: 10.3389/fgene.2020.605054. eCollection 2020.

In silico Prediction of miRNA Interactions With Candidate Atherosclerosis Gene mRNAs

Dina Mukushkina  1 , Dana Aisina  1 , Anna Pyrkova  1 , Alma Ryskulova  2 , Siegfried Labeit  3 , Anatoliy Ivashchenko  1
Affiliations

In silico Prediction of miRNA Interactions With Candidate Atherosclerosis Gene mRNAs

Dina Mukushkina et al. Front Genet. .

Abstract

The involvement of genes and miRNAs in the development of atherosclerosis is a challenging problem discussed in recent publications. It is necessary to establish which miRNAs affect the expression of candidate genes. We used known candidate atherosclerosis genes to predict associations. The quantitative characteristics of interactions of miRNAs with mRNA candidate genes were determined using the program, which identifies the localization of miRNA binding sites in mRNA, the free energy interaction of miRNA with mRNA. In mRNAs of GAS6 and NFE2L2 candidate genes, binding sites of 21 miRNAs and of 15 miRNAs, respectively, were identified. In IRS2 mRNA binding sites of 25 miRNAs were located in a cluster of 41 nt. In ADRB3, CD36, FASLG, FLT1, PLA2G7, and PPARGC1A mRNAs, clusters of miR-466, ID00436.3p-miR, and ID01030.3p-miR BS were identified. The organization of overlapping miRNA binding sites in clusters led to their compaction and caused competition among the miRNAs. The binding of 53 miRNAs to the mRNAs of 14 candidate genes with free energy interactions greater than -130 kJ/mole was determined. The miR-619-5p was fully complementary to ADAM17 and CD36 mRNAs, ID01593.5p-miR to ANGPTL4 mRNA, ID01935.5p-miR to NFE2L2, and miR-5096 to IL18 mRNA. Associations of miRNAs and candidate atherosclerosis genes are proposed for the early diagnosis of this disease.

Keywords: association; atherosclerosis; binding sites cluster; gene; mRNA; marker; miRNA.

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Figures

FIGURE 1
FIGURE 1
The WebLogo schemes (https://weblogo.berkeley.edu/logo.cgi) of nucleotide sequences for BS clusters in mRNA of GAS6 (A), NFE2L2 (B), SCAP (C) orthological genes. Nucleotides of BS clusters are highlighted in blue. Nucleotides of BS clusters mRNA of GAS6 Ggo (Gîrillà gîrillà), Hsa (Homo sapiens), Mmu (Macaca mulatta), Pab (Pongo abelii), Pan (papio anubis), Ptr (pan troglodytes); nucleotides of BS clusters mRNA of NFE2L2 Ggo, Hsa, Pab, Pan, Ptr; nucleotides of BS clusters mRNA of SCAP Ggo, Hsa, Mmu, Pab, Pan, Ptr.
FIGURE 2
FIGURE 2
Convincing evidence of the effectiveness of the MirTarget program in determining the characteristics of miRNA binding to the 5′ UTR, CDS and 3′ UTR of mRNA. The diagrams show the interaction of nucleotides along the entire length of the miRNA in the BS of the target mRNA and the characteristics of this interaction. Non-canonical base pairs are in bold.
See this image and copyright information in PMC

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