microRNAs in the Same Clusters Evolve to Coordinately Regulate Functionally Related Genes
microRNAs in the Same Clusters Evolve to Coordinately Regulate Functionally Related Genes
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同一簇中的 microRNA 进化以协调调节功能相关基因
DOI：
10.1093/molbev/msw089
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发表时间：
2016-09-01
影响因子：
10.7
通讯作者：
Lu, Jian
中科院分区：
文献类型：
--
作者：
Wang, Yirong;Luo, Junjie;Lu, Jian
microRNA（miRNAs）是一类内源性表达的小分子非编码RNA。动物miRNA的基因组位置显著地聚集在离散的基因座中。我们发现复制和从头形成是产生miRNA簇的重要机制，并且成簇的miRNA往往在进化上保守。我们提出了一个“功能性共适应”模型来解释聚类如何帮助新出现的miRNAs生存和发展功能。我们提出的证据表明，在同一簇中的miRNAs的丰度是高度相关的，这些miRNAs对人体组织中的靶基因产生协同抑制作用。通过将miRNAs转染到人类和果蝇细胞中，并通过深度测序广泛分析转录组的改变，我们进一步证明了miR-17-92簇中新旧miRNAs之间的功能性共适应。我们的群体基因组分析表明，积极的达尔文选择可能是miRNA聚类形成和进化的驱动力。我们的模型为miRNA聚类的机制和进化意义提供了新的见解。
MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs. The genomic locations of animal miRNAs are significantly clustered in discrete loci. We found duplication and de novo formation were important mechanisms to create miRNA clusters and the clustered miRNAs tend to be evolutionarily conserved. We proposed a " functional coadaptation" model to explain how clustering helps newly emerged miRNAs survive and develop functions. We presented evidence that abundance of miRNAs in the same clusters were highly correlated and those miRNAs exerted cooperative repressive effects on target genes in human tissues. By transfecting miRNAs into human and fly cells and extensively profiling the transcriptome alteration with deep-sequencing, we further demonstrated the functional co-adaptation between new and old miRNAs in the miR-17-92 cluster. Our population genomic analysis suggest that positive Darwinian selection might be the driving force underlying the formation and evolution of miRNA clustering. Our model provided novel insights into mechanisms and evolutionary significance of miRNA clustering.