Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression.

Moldir Myrzabekova,Siegfried Labeit,Aigul Akimniyazova,Raigul Niyazova,Anatoliy Ivashchenko

doi:10.3389/fgene.2021.705350

Abstract

Milk and other products from large mammals have emerged during human evolution as an important source of nutrition. Recently, it has been recognized that exogenous miRNAs (mRNA inhibited RNA) contained in milk and other tissues of the mammalian body can enter the human body, which in turn have the ability to potentially regulate human metabolism by affecting gene expression. We studied for exogenous miRNAs from Bos taurus that are potentially contain miRNAs from milk and that could act postprandially as regulators of human gene expression. The interaction of 17,508 human genes with 1025 bta-miRNAs, including 245 raw milk miRNAs was studied. The milk bta-miR-151-5p, bta-miR-151-3p, bta-miRNA-320 each have 11 BSs (binding sites), and bta-miRNA-345-5p, bta-miRNA-614, bta-miRNA-1296b and bta-miRNA-149 has 12, 14, 15 and 26 BSs, respectively. The bta-miR-574-5p from cow’s milk had 209 human genes in mRNAs from one to 25 repeating BSs. We found 15 bta-miRNAs that have 100% complementarity to the mRNA of 13 human target genes. Another 12 miRNAs have BSs in the mRNA of 19 human genes with 98% complementarity. The bta-miR-11975, bta-miR-11976, and bta-miR-2885 BSs are located with the overlap of nucleotide sequences in the mRNA of human genes. Nucleotide sequences of BSs of these miRNAs in 5′UTR mRNA of human genes consisted of GCC repeats with a total length of 18 nucleotides (nt) in 18 genes, 21 nt in 11 genes, 24 nt in 14 genes, and 27–48 nt in nine genes. Nucleotide sequences of BSs of bta-miR-11975, bta-miR-11976, and bta-miR-2885 in CDS mRNA of human genes consisted of GCC repeats with a total length of 18 nt in 33 genes, 21 nt in 13 genes, 24 nt in nine genes, and 27–36 nt in 11 genes. These BSs encoded polyA or polyP peptides. In only one case, the polyR (SLC24A3 gene) was encoded. The possibility of regulating the expression of human genes by exogenous bovine miRNAs is discussed.

Highlights

The miRNAs are 18–24-nucleotide-long RNA nanoscale molecules that are highly conserved among species
MirTarget differs from other programs in terms of finding the BSs of miRNA on the mRNAs of plant genes (Dai et al, 2011) in that 1) it takes into account the interaction of the miRNA with mRNA over the entire miRNA sequence; 2) it takes into account non-canonical pairs G–U and A–C; and 3) it calculates the free energy of the interaction of the miRNA with mRNA, and when two or more miRNAs are bound with one mRNA or, if the BSs of two different miRNAs coincide in part, the preferred miRNA binding site is considered to be the one for which the free binding energy is greater
Exogenous miRNAs can be ingested with raw food, and this pathway of miRNA transmission is preserved in nature during evolution

Summary

Introduction

The miRNAs (mRNA inhibited RNA) are 18–24-nucleotide-long RNA nanoscale molecules that are highly conserved among species They regulate post-transcriptional gene expression either by inhibiting mRNA translation or by degrading through exonuclease action Humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of cow’s milk; these miRNAs enter peripheral blood mononuclear cells and presumably other peripheral tissues, and physiological concentrations of milk miRNAs may affect human gene expression in vivo and in cell cultures (Baier et al, 2014; Lukasik and Zielenkiewicz, 2014; Shu et al, 2015; Yim et al, 2016)

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