MicroRNA duplication accelerates the recruitment of new targets during vertebrate evolution.

MicroRNA duplication accelerates the recruitment of new targets during vertebrate evolution.
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MicroRNA 复制加速了脊椎动物进化过程中新靶标的招募。

DOI:
10.1261/rna.062752.117
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发表时间:
2018-06
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Lu J
Lu J
中科院分区:
其他
文献类型:
--
作者:
Luo J;Wang Y;Yuan J;Zhao Z;Lu J

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在后生动物的进化过程中,miRNAs的库已经大大扩展,并且复制是产生新的功能性miRNAs的重要机制。然而,对于旁系同源miRNA之间的功能差异以及重复miRNA与基因组环境之间可能的协同进化知之甚少。通过系统地检查各种人体组织中的小RNA表达谱,并询问公开可用的miRNA:mRNA配对嵌合体,我们发现,在脊椎动物中,重复的miRNA的表达模式和靶向偏好的变化是普遍的。经验相互作用和靶点预测表明,与单拷贝miRNA相比,进化上保守的同源种子重复miRNA与显著更高数量的靶位点配对。我们的出生和死亡进化分析表明,新的miRNAs靶位点在功能发育过程中经历了频繁的获得和丧失。我们的研究结果表明,如果一个新出现的靶位点与多个旁系同源miRNA共享的种子配对,而不是与一个单拷贝miRNA配对,那么它有更高的可能性是功能性的,并通过自然选择得到维持。我们通过将let-7a和let-7 b模拟物转染到四种哺乳动物的肾脏来源的细胞系中,并通过广泛的高通量测序测量所得的转录组改变,实验验证了两种旁系同源miRNA之间靶抑制的差异。我们的研究结果还表明,let-7靶位点的获得和丧失可能与哺乳动物物种中let-7抑制性的进化有关。
The repertoire of miRNAs has considerably expanded during metazoan evolution, and duplication is an important mechanism for generating new functional miRNAs. However, relatively little is known about the functional divergence between paralogous miRNAs and the possible coevolution between duplicated miRNAs and the genomic contexts. By systematically examining small RNA expression profiles across various human tissues and interrogating the publicly available miRNA:mRNA pairing chimeras, we found that changes in expression patterns and targeting preferences are widespread for duplicated miRNAs in vertebrates. Both the empirical interactions and target predictions suggest that evolutionarily conserved homo-seed duplicated miRNAs pair with significantly higher numbers of target sites compared to the single-copy miRNAs. Our birth-and-death evolutionary analysis revealed that the new target sites of miRNAs experienced frequent gains and losses during function development. Our results suggest that a newly emerged target site has a higher probability to be functional and maintained by natural selection if it is paired to a seed shared by multiple paralogous miRNAs rather than being paired to a single-copy miRNA. We experimentally verified the divergence in target repression between two paralogous miRNAs by transfecting let-7a and let-7b mimics into kidney-derived cell lines of four mammalian species and measuring the resulting transcriptome alterations by extensive high-throughput sequencing. Our results also suggest that the gains and losses of let-7 target sites might be associated with the evolution of repressiveness of let-7 across mammalian species.
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