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Dynamic evolution of mir-17–92 gene cluster and related miRNA gene families in vertebrates

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Abstract

mir-17–92 gene cluster is widely distributed in vertebrates and plays an important role in regulating multiple biological processes. Its dysregulation may be associated with risk of some human cancers. The microRNA (miRNA) members are identified in the three gene families: mir-17, mir-19 and mir-25. Herein we attempted to understand the evolutionary processes and patterns in vertebrates. The three miRNA gene families showed difference in distribution, number of miRNA genes and clustered miRNA genes in the five animal species. Compared to other related gene clusters, mir-17–92 cluster was well-conserved and had more abundant roles in multiple biological processes. These clustered miRNAs showed inconsistent nucleotide divergence patterns across different animal species, even between homologous miRNA genes. Simultaneously, they also indicated inconsistent expression patterns although they were co-transcribed as a polycistronic transcript. Phylogenetic tree based on human pre-miRNA sequences showed that mir-19 gene family was an older miRNA species, while tree based on miRNA gene cluster indicated evolutionary positions of different animal species. The study shows dynamic evolution of the mir-17–92 gene cluster and related miRNA gene families across vertebrates, which may be derived from potential functional implication. miRNA gene cluster should be a better phylogenetic marker than a single miRNA gene to reveal functional and evolutionary relationships.

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Acknowledgments

We thank Professor Pengcheng Xun for editing the manuscript. The work was supported by National Natural Science Foundation of China (No. 30901232, 81072389 and 81102182), China Postdoctoral Science Foundation funded project (No. 2012M521100), the Research Found for the Doctoral Program of Higher Education of China (No. 211323411002), key Grant of Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 10KJA33034), Jiangsu Planned Projects for Postdoctoral Research Funds (No. 1201022B), Science and Technology Development Fund Key Project of Nanjing Medical University (No. 2012NJMU001), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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The authors declare no potential conflict of interests with respect to the authorship and/or publication of this paper.

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Correspondence to Feng Chen.

Electronic supplementary material

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11033_2012_2388_MOESM1_ESM.tif

Supplementary material 1 Fig. S1 Secondary structures of the three human gene clusters based on minimum free energy prediction by using RNAfold WebServer. (TIFF 954 kb)

11033_2012_2388_MOESM2_ESM.tif

Supplementary material 2 Fig. S2 Multiple sequence alignment of known miR-#-3p (A) and miR-#-5p (B) in hsa-mir-25 gene family, also including hsa-mir-363. Compared to miR-#-5p, another miRNA product is well-conserved across different miRNA species, especially for the “seed sequences” (nucleotides 2-8). (TIFF 789 kb)

11033_2012_2388_MOESM3_ESM.tif

Supplementary material 3 Fig. S3 A network shows miR-17–92 gene cluster plays important roles in multiple biological processes. miRNA members in hsa-mir-17–92 gene cluster, have abundant roles in biological processes. Here, these experimental validated target genes are regulated by at least two miRNAs. (TIFF 3227 kb)

11033_2012_2388_MOESM4_ESM.tif

Supplementary material 4 Fig. S4 Stem-loop structures of mir-92a in the five animal species. Due to involved nucleotide divergences across these pre-miRNAs, their secondary structures show difference, although their mature miRNAs are well-conserved with the consensus sequences (pink sequences). The loop sequences have significant difference in length and structure. (TIFF 461 kb)

11033_2012_2388_MOESM5_ESM.tif

Supplementary material 5 Fig. S5 Expression pattern of the miR-17–92 gene cluster based on published literatures. Relative expression levels of miRNA members in gene cluster are estimated based on percentage. Inconsistent expression pattern is detected in control, mild and severe human pre-eclampsia samples (A), and between layer chickens (bred for egg production) and Broiler chickens (bred for meat pro-duction) (B), although these miRNAs are co-transcribed as a polycistronic transcript. (TIFF 246 kb)

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Guo, L., Yang, S., Zhao, Y. et al. Dynamic evolution of mir-17–92 gene cluster and related miRNA gene families in vertebrates. Mol Biol Rep 40, 3147–3153 (2013). https://doi.org/10.1007/s11033-012-2388-z

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  • DOI: https://doi.org/10.1007/s11033-012-2388-z

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