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. 2015 Jan;3(1):30-9.
doi: 10.1002/mgg3.110. Epub 2014 Sep 15.

Genetic variability of microRNA regulome in human

Jana Obsteter  1 , Peter Dovc  1 , Tanja Kunej  1
Affiliations

Genetic variability of microRNA regulome in human

Jana Obsteter et al. Mol Genet Genomic Med. 2015 Jan.

Abstract

MicroRNAs are currently being extensively studied due to their important role as post-transcriptional regulators. During miRNA biogenesis, precursors undergo two cleavage steps performed by Drosha-DGCR8 (Microprocessor) cleaving of pri-miRNA to produce pre-miRNA and Dicer-mediated cleaving to create mature miRNA. Genetic variants within human miRNA regulome have been shown to influence miRNA expression, target interaction and to affect the phenotype. In this study, we reviewed the literature, existing bioinformatics tools and catalogs associated with polymorphic miRNA regulome, and organized them into four categories: (1) polymorphisms located within miRNA genes (miR-SNPs), (2) transcription factor-binding sites/miRNA regulatory regions (miR-rSNPs), (3) miRNA target sites (miR-TS-SNPs), and 4. miRNA silencing machinery (miR-SM-SNPs). Since the miR-SM-SNPs have not been systematically studied yet, we have collected polymorphisms associated with miRNA silencing machinery. We have developed two catalogs containing genetic variability within: (1) genes encoding three main catalytic components of the silencing machinery, DROSHA, DGCR8, and DICER1; (2) miRNA genes itself, overlapping Drosha and Dicer cleavage sites. The developed resource of polymorphisms is available online (http://www.integratomics-time.com/miRNA-regulome) and will be useful for further functional studies and development of biomarkers associated with diseases and phenotypic traits.

Keywords: Biogenesis; Dicer; Drosha; human; microRNA (miRNA); polymorphisms.

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Figures

Figure 1
Figure 1
Flowchart of study assembly and aims of the study.
Figure 2
Figure 2
Categories of genetic variability associated with miRNAs.
Figure 3
Figure 3
The number of nonsynonymous polymorphisms within genes encoding silencing machinery (DROSHA, DGCR8, DICER1) and the number of polymorphisms within Drosha and Dicer cleavage sites.
Figure 4
Figure 4
Nucleotide sequences of miRNA genes containing MNPs (DNP or TNP) overlapping Drosha (A) or Dicer (B) cleavage sites.
Figure 5
Figure 5
MicroRNA genes with polymorphisms overlapping both, Drosha and Dicer cleavage sites.
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