A mixed antagonistic/synergistic miRNA repression model enables accurate predictions of multi-input miRNA sensor activity.
A mixed antagonistic/synergistic miRNA repression model enables accurate predictions of multi-input miRNA sensor activity.
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DOI：
10.1038/s41467-018-04575-0
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发表时间：
2018-06-22
影响因子：
16.6
通讯作者：
Weiss R
中科院分区：
文献类型：
--
作者：
Gam JJ;Babb J;Weiss R
microRNAs（miRNAs）调节大多数蛋白质编码基因，影响几乎所有的生物学途径。然而，基于miRNA的调控的定量维度尚未完全理解。特别是，miRNA靶位点位置的影响，多个靶位点的组成规则，以及由许多miRNA调控的基因的协同性限制尚未定量表征。我们探索这些方面的miRNA生物学在一个定量的单细胞水平上使用的620个miRNA传感器和记者，在不同的位置，许多miRNA靶位点的调控库。有趣的是，我们发现，在同一个非翻译区的miRNA靶位点集表现出联合的miRNA活性描述的拮抗关系，而在不同的非翻译区显示协同作用。所得到的拮抗/协同计算模型使得能够高保真预测包含许多miRNA靶标的传感器的miRNA传感器活性。这些发现可能有助于加速用于临床和研究应用的复杂传感器的开发。microRNA（miRNAs）是基因表达的重要转录后调节因子，但miRNAs生物学的许多定量方面仍有待阐明。基于一个miRNA传感器库，作者在单细胞水平上量化了miRNA的调控，并开发了一个预测miRNA靶点相互作用的模型。
MicroRNAs (miRNAs) regulate a majority of protein-coding genes, affecting nearly all biological pathways. However, the quantitative dimensions of miRNA-based regulation are not fully understood. In particular, the implications of miRNA target site location, composition rules for multiple target sites, and cooperativity limits for genes regulated by many miRNAs have not been quantitatively characterized. We explore these aspects of miRNA biology at a quantitative single-cell level using a library of 620 miRNA sensors and reporters that are regulated by many miRNA target sites at different positions. Interestingly, we find that miRNA target site sets within the same untranslated region exhibit combined miRNA activity described by an antagonistic relationship while those in separate untranslated regions show synergy. The resulting antagonistic/synergistic computational model enables the high-fidelity prediction of miRNA sensor activity for sensors containing many miRNA targets. These findings may help to accelerate the development of sophisticated sensors for clinical and research applications. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression but many quantitative aspects of miRNA biology remain to be elucidated. Based on a library of miRNA sensors, the authors quantify miRNA regulation at single cell level and develop a model to predict miRNA target interactions.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1002/bies.201400191
发表时间：
2015-04
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
Ebert, Margaret S.;Neilson, Joel R.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.