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Binding sites of miRNAs with transcription factors' genes of Camelus ferus and Homo sapiens A.T. Ivashchenko, A.Z. Alybaeva, R.Y. Niyazova
Institute of Biology and Biotechnology Problems, al-Farabi KazNU, 050038, Kazakhstan, a_ivashchenko@mail.ru

The nucleotide sequences of mRNAs of ZNF family 157 TF genes of Camelus ferus were taken from GenBank (http://www.ncbi.nlm.nih.gov). The nucleotide sequences of 2563 hsamiRNAs were taken from the miRBase database (http://mirbase.org). We next evaluated human miRNAs since camel miRNAs have not yet been identified. The search for miRNA binding sites in target gene mRNAs was performed using the MirTarget program. This program defines: the beginning of binding sites of miRNAs with mRNAs; the location of sites in the 5'-untranslated region (5'UTR), a protein-coding portion (CDS) and the 3'untranslated region (3'UTR) of mRNA; the free energy of hybridization (G, kJ/mole) and patterns of interaction miRNAs nucleotides with mRNAs. We expected value of G/Gm (%), where Gm is the free energy of miRNA binding with fully complementary nucleotide sequence. Binding sites of miRNAs with mRNAs selected with the value of G/Gm equal or more than 90%. The position of the binding sites was shown from the first nucleotide (n.) of mRNA. We searched for the binding sites of 2,563 Homo sapiens genome miRNAs and the mRNA of 157 Camelus ferus zinc finger family transcription factor (ZNF family TF) genes. The table 1 shows the characteristics of some of the miRNAs that bind to human orthologous transcription factors of the ZNF family of C. ferus and H. sapiens. There are 16 binding sites in the 5 UTRs, 210 binding sites in the CDSs, and 34 binding sites in the 3 UTRs of 96 transcription factor gene mRNAs. Eight miRNAs bind to the mRNA of the Gli2 gene, and there are seven miRNA binding sites in the ZNF236 and GLIS1 mRNAs. In the 3 UTR of the ZFP91 mRNA, 13 binding sites for miR-574-5p were identified, located through two nucleotides. The VEZF1 gene mRNA has eight binding sites for miR-1322, located through three nucleotides. miRNAs that are 25 and 26 nucleotides in length have the greatest binding energy. The G/Gm values, which characterize the degree of affinity of miRNAs to mRNA,


vary from 90% to 96% in these miRNAs. miR-1322 has one binding site in the mRNA of Gli1, HINFP, HIVEP1, MTF1, SALL4, SP1, ZNF335 and ZNF451 target genes, two sites in the ZNF142 mRNA, and three sites in the EGR1 mRNA. The G values ranged from -114.6 kJ/mole to -138.0 kJ/mole. Some miRNAs that are 23 and 24 nucleotides in length also have high G values, which range from -112.5 kJ/mole to -129.5 kJ/mole. The results demonstrate a strong dependence of transcription factor gene expression on their associated miRNAs. Table 1. The characteristics of miRNA binding sites in mRNAs of transcription factor genes of ZNF family Gene miRNA Position in mRNA, n. G/Gm, % C.ferus/H.sapiens C.ferus/H.sapiens E4F1 miR-6861-3p 1037/1205 92/92 EGR1 miR-4318 454/689 93/93 EGR4 miR-6867-3p 182/1253 92/92 GFI1 miR-4481 43/293 93/93 GLI2 miR-665 454/466 93/94 GLI2 miR-6763-5p 3650/4313 92/92 HINFP miR-877-3p 146/384 93/95 KLF4 miR-4478 394/969 91/93 KLF9 miR-4492 289/1646 94/94 MECOM miR-466 5158/5100 93/95 PLAGL2 miR-4279 203/306 93//93 PRDM10 miR-4516 2861/724 91/94 TRERF1 miR-3960 1669/2253 93/93 WIZ miR-1260a 182/396 94/94 WIZ miR-7155-3p 497/711 92/92 ZFPM1 miR-1306-3p 942/1020 94/91 ZKSCAN4 miR-6828-3p 899/1143 94/94 ZNF143 miR-4313 25/25 93/93 ZNF335 miR-548av-5p 1366/1468 95/95 ZNF423 miR-3155b 2918/3236 92/92 ZNF652 miR-6892-5p 1946/2150 96/91 The data show great similarity to the affinity of orthologous mRNAs of camel and human transcription factor genes. The vast majority of binding sites are located in the protein coding portions of the mRNAs, indicating that regulation of the expression of transcription factor genes by miRNAs is evolutionarily conserved.


Orthologous miRNAs of Equus caballus and Bos taurus interacted with mRNAs orthologous to the MYB family of transcription factors, which also indicates that regulation of transcription factor gene expression by miRNAs is evolutionarily conserved across the species studied.