An allelic series of miR-17 ∼ 92-mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron.
An allelic series of miR-17 ∼ 92-mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron.
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DOI：
10.1038/ng.3321
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发表时间：
2015-07
期刊：
影响因子：
30.8
通讯作者：
Ventura, Andrea
中科院分区：
文献类型：
--
作者：
Han, Yoon-Chi;Vidigal, Joana A.;Mu, Ping;Yao, Evelyn;Singh, Irtisha;Gonzalez, Alvaro J.;Concepcion, Carla P.;Bonetti, Ciro;Ogrodowski, Paul;Carver, Brett;Selleri, Licia;Betel, Doron;Leslie, Christina;Ventura, Andrea
多顺反子microRNA簇是脊椎动物基因组的共同特征。属于不同种子家族的miRNA从单个转录单位的协调表达表明功能合作，但这一假设尚未得到实验验证。在这里，我们报告了一个等位基因系列的基因工程小鼠携带选择性靶向删除的个别组件的miR-17~92的表征。我们的研究结果证明了该簇成员之间的功能合作和专业化的共存，确定了miR-17种子家族在脊椎动物中控制轴向模式的新功能，并表明miR-19的缺失选择性地损害了两种人类癌症模型中Myc驱动的肿瘤发生。通过整合表型分析和基因表达谱分析，我们提供了一个全基因组的多顺反子miRNA簇的组成部分如何影响体内基因表达的观点。本文报道的试剂和数据集将加速探索这一重要miRNA簇的复杂生物学功能。
Polycistronic microRNA clusters are a common feature of vertebrate genomes. The coordinated expression of miRNAs belonging to different seed families from a single transcription unit suggests functional cooperation, but this hypothesis has not been experimentally tested. Here we report the characterization of an allelic series of genetically engineered mice harboring selective targeted deletions of individual components of miR-17~92. Our results demonstrate the co-existence of functional cooperation and specialization among members of this cluster, identify a novel function for the miR-17 seed family in controlling axial patterning in vertebrates, and show that loss of miR-19 selectively impairs Myc-driven tumorigenesis in two models of human cancer. By integrating phenotypic analysis and gene expression profiling, we provide a genome-wide view of how components of a polycistronic miRNA-cluster affect gene expression in vivo. The reagents and datasets reported here will accelerate exploration of the complex biological functions of this important miRNA cluster.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
64.8
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通讯作者：
Lewis, J
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作者：
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通讯作者：
Tuschl, Thomas
影响因子：
64.8
作者：
Chapman, DL;Papaioannou, VE
通讯作者：
Papaioannou, VE