Genetic variability of micro RNA regulome in human

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.

Genetic Variability of MicroRNA Genes in 15 Animal Species

“…Changes in miRNA expression and miRNA regulome polymorphisms have been associated with phenotypic traits and diseases 5 , 6 . Therefore a systematic screening for miRNA gene variability could contribute to a development of new potential biomarkers associated to phenotype variability.…”

MicroRNA-Related Polymorphisms in Infectious Diseases—Tiny Changes With a Huge Impact on Viral Infections and Potential Clinical Applications

“…Next, the mature single-stranded miRNA and the Argonaut protein (AGO) constitute a multicomponent complex called RNA-induced silencing complex, which allows the binding to complementary sequences in the 3′ untranslated region (3′UTR) of a target mRNA, leading to translational repression or degradation of the mRNA ( 7 , 16 – 18 ). The key binding point for miRNA–mRNA interaction is the seed region, located within nucleotides 2–8 from the 5′ end of the mature miRNA sequence ( 19 , 20 ). In general, a partial complementarity of the mRNA 3′UTR to the miRNA seed sequence leads to translational inhibition, while a perfect complementarity results in mRNA degradation.…”

Regulatory RNAs and Cardiovascular Disease – With a Special Focus on Circulating MicroRNAs

“…The miRNA regulome is defined as the compendium of regulatory elements that either regulate miRNA expression (transcriptional control elements and pre-miRNAs) or are regulated by miRNA activity (RNA target sites). Genetic variation in the miRNA regulome can perturb miRNA expression and/or function, potentially contributing to disease development and a wide variety of lipid-related phenotypes (Sethupathy 2013, Obsteter et al 2015. Advancements in the miRNA field indicate the clear involvement of miRNAs and genetic variations within the miRNA pathway in the progression and prognosis of many diseases, including atherosclerotic cardiovascular diseases.…”

“…The miRNAs then pair with mRNAs by binding to different target-gene regions: the 3′-untranslated region (3′UTR), 5′UTR, and promoter or coding sequences that repress or activate translation. The crucial binding location for translational regulation resides in the mature miRNA sequence, more accurately within the nucleotides 2-7 or 2-8 from the 5′ end of the miRNA, called the seed region (Obsteter et al 2015). The mechanisms by which miRNAs reduce protein output are mostly triggered either by deadenylation of the target mRNA and inhibition of eukaryotic initiation factors, or by interference with translational elongation.…”