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Effects of genetic variations on microRNA: target interactions

机译:遗传变异对microRNA的影响:靶标相互作用

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Genetic variations within microRNA (miRNA) binding sites can affect miRNA-mediated gene regulation, which may lead to phenotypes and diseases. We perform a transcriptome-scale analysis of genetic variants and miRNA: target interactions identified by CLASH. This analysis reveals that rare variants tend to reside in CDSs, whereas common variants tend to reside in the 3' UTRs. miRNA binding sites are more likely to reside within those targets in the transcriptome with lower variant densities, especially target regions in which nucleotides have low mutation frequencies. Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA: target hybridization but also the structural accessibility of the binding sites and flanking regions. These suggest an interpretation for certain associations between genetic variants and diseases, i. e. modulation of miRNA-mediated gene regulation by common or rare variants within or near miRNA binding sites, likely through target structure alterations. Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.
机译:microRNA(miRNA)结合位点内的遗传变异会影响miRNA介导的基因调控,这可能导致表型和疾病。我们进行了遗传变异和miRNA的转录组规模分析:CLASH鉴定的靶标相互作用。该分析表明,罕见的变体倾向于驻留在CDS中,而常见的变体倾向于驻留在3'UTR中。 miRNA结合位点更有可能驻留在转录组中具有较低变异密度的那些靶标内,尤其是核苷酸突变频率较低的靶标区域。此外,在miRNA结合位点之内或附近的绝大多数遗传变异不仅可以改变miRNA:靶标杂交的潜力,而且可以改变结合位点和侧翼区域的结构可及性。这些建议解释了遗传变异与疾病之间的某些联系,即。 e。在miRNA结合位点内或附近的常见或罕见变体对miRNA介导的基因调节的调控,可能是通过靶结构的改变。我们的数据将有助于发现miRNA,遗传变异和人类疾病之间的新关联。

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