The regulatory activity of microRNA☆ species has substantial influence on microRNA and 3′ UTR evolution
The regulatory activity of microRNA☆ species has substantial influence on microRNA and 3′ UTR evolution
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DOI：
10.1038/nsmb.1409
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发表时间：
2008-04-01
影响因子：
16.8
通讯作者：
Lai, Eric C.
中科院分区：
文献类型：
--
作者：
Okamura, Katsutomo;Phillips, Michael D.;Lai, Eric C.
在microRNA（miRNA）生物发生过程中，与21-22个核苷酸的RNA双链体相似的一条链被优先选择进入沉默复合物。另一条链称为miRNA*，通常被认为是载体链。在这里，我们表明，虽然果蝇的miRNA* 种类比他们的合作伙伴少，他们往往存在于生理相关的水平，可以与Argonaute蛋白。比较基因组分析显示，超过40%的miRNA* 序列抵抗果蝇进化中的核苷酸差异，并且这些高度保守的miRNA* 物种中至少有一半选择保守的3'非翻译区种子匹配，远高于背景噪音。最后，我们验证了miRNA* 种类在培养细胞和转基因动物中的抑制活性。这些数据拓宽了miRNA调控网络的范围，并提出了在进化过程中使miRNA功能多样化的重要机制。
During microRNA (miRNA) biogenesis, one strand of a similar to 21-22-nucleotide RNA duplex is preferentially selected for entry into a silencing complex. The other strand, known as the miRNA* species, has typically been assumed to be a carrier strand. Here we show that, although Drosophila melanogaster miRNA* species are less abundant than their partners, they are often present at physiologically relevant levels and can associate with Argonaute proteins. Comparative genomic analyses revealed that > 40% of miRNA* sequences resist nucleotide divergence across Drosophilid evolution, and at least half of these well-conserved miRNA* species select for conserved 3' untranslated region seed matches well above background noise. Finally, we validated the inhibitory activity of miRNA* species in both cultured cells and transgenic animals. These data broaden the reach of the miRNA regulatory network and suggest an important mechanism that diversifies miRNA function during evolution.