Structural dynamics control the MicroRNA maturation pathway.
Structural dynamics control the MicroRNA maturation pathway.
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DOI：
10.1093/nar/gkw793
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发表时间：
2016-11-16
影响因子：
14.9
通讯作者：
Major F
中科院分区：
文献类型：
--
作者：
Dallaire P;Tan H;Szulwach K;Ma C;Jin P;Major F
microRNAs（miRNAs）是重要的基因表达调控因子，是许多疾病发生发展的一级嫌疑分子。癌细胞表达数据的比较分析突出了许多失调的miRNA。miR-125 a低表达与乳腺癌预后不良有关。有趣的是，miR-125 a的单核苷酸多态性（SNP）位于乳腺癌患者表达的次要等位基因内。预计SNP不会影响初级转录物或前体的基态结构，但RT-qPCR检测不到前体或成熟产物。该SNP如何调节miR-125 a的成熟尚不清楚。在这里，建立在来自核磁共振研究的RNA动力学模型的基础上，我们开发了一个定量模型，使瞬态结构网络的可视化和比较。我们观察到变异体网络与其各自野生型网络之间的距离及其相对成熟度与后者之间的高度相关性，表明瞬时结构在miRNA稳态中的重要作用。我们根据瞬时结构网络之间的成对距离对人类miRNA进行分类。
MicroRNAs (miRNAs) are crucial gene expression regulators and first-order suspects in the development and progression of many diseases. Comparative analysis of cancer cell expression data highlights many deregulated miRNAs. Low expression of miR-125a was related to poor breast cancer prognosis. Interestingly, a single nucleotide polymorphism (SNP) in miR-125a was located within a minor allele expressed by breast cancer patients. The SNP is not predicted to affect the ground state structure of the primary transcript or precursor, but neither the precursor nor mature product is detected by RT-qPCR. How this SNP modulates the maturation of miR-125a is poorly understood. Here, building upon a model of RNA dynamics derived from nuclear magnetic resonance studies, we developed a quantitative model enabling the visualization and comparison of networks of transient structures. We observed a high correlation between the distances between networks of variants with that of their respective wild types and their relative degrees of maturation to the latter, suggesting an important role of transient structures in miRNA homeostasis. We classified the human miRNAs according to pairwise distances between their networks of transient structures.
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