Features of miRNAs binding sites within the C2H2 ZNF family: а Bos taurus, Eqqus caballus, and Ovies aries comparative approach

Abstract

C2H2 zinc finger genes constitute the largest class of transcription factors in humans and one of the largest gene families in mammals. Using the MirTarget program, we predicted miRNA binding sites (BSs) in CDS, 5’UTR and 3’UTR mRNAs of the ZNF family transcription factors genes of Bos (B.) taurus, Equus (E.) caballus, Ovis (O.) aries. We studied interactions of 1025 B.taurus miRNAs with 315 mRNAs of zf-C2H2 transcription factors family genes. From established 442 BSs, 196 are located in CDS, 164 in 3’UTR, 82 in 5’UTR. The free binding energy values range from -83 to -127 kJ/mol. mRNAs of several genes have miRNA BSs with overlapping nucleotide sequences (clusters). The cluster of BSs of miR-11975, miR-11976 and miR-2885 were found in 5’UTR, 3’UTR and CDS mRNAs of FEZF1, SP8, VEZF1, PRDM6, SP3, ZNF366, PRDM13, PRDM12, ZIC4 and ZFP91 genes. Multiple BSs were predicted for miR-574 in mRNAs of HIVEP2, KLF7, SNAI2, SP4, ZNF677, ZNF710, ZFP91 genes. We studied binding characteristics between 690 miRNAs and 257 mRNAs of E.qaballus zf-C2H2 TFs family genes. The free binding energy ΔG values varied between -87 and -129 kJ/mol. From established 60 BSs, 24 are located in CDS, 21 in 5’UTR, 15 in 3’UTR. The largest ΔG value determined for binding of miR-8996 with
PRDM16 mRNA equals to -129 kJ/mol. The interaction of 152 miRNAs with 223 mRNAs of O.aries zf- C2H2 transcription factors genes was identified. The free binding energy values varied in between -85 and -117 kJ/mol. 18 BSs were found in mRNAs of TFs genes, located in CDS and 3’UTR. Therefore, our data suggests that regulation of zf-C2H2 transcription factors by miRNAs may involve their coding regions, thus providing a novel level of complexity when decoding the complex mechanism of miRNA/mRNA interplay and when interpreting conserved motifs within ZF coding sequences.