Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets.
Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets.
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DOI：
10.1093/nar/gkw164
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发表时间：
2016-04-20
影响因子：
14.9
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Cass AA;Bahn JH;Lee JH;Greer C;Lin X;Kim Y;Hsiao YH;Xiao X
在哺乳动物中，小 RNA 在转录后基因调控中发挥着重要作用。虽然它们在 mRNA 不稳定和翻译抑制中的作用已广为人知，但它们在靶 RNA 的核酸内切裂解中的作用却知之甚少。目前已知很少有 microRNA 可以指导 RNA 切割。内源性小干扰 RNA 有望诱导靶点切割，但其靶基因仍然很大程度上未知。我们通过对小 RNA 和降解组测序数据的综合分析，对小鼠中小 RNA 介导的核酸内切裂解进行了系统研究，而不对已知的小 RNA 施加任何偏见。鉴定了数百个小RNA切割诱导RNA及其同源靶基因，显着扩展了已知小RNA引导切割事件的库。引人注目的是，小 RNA 及其靶位点都与逆转录转座子显着重叠，这为长期以来的推测提供了证据，即 mRNA 中的逆转录转座元件可用作基因靶向的信号。此外，我们的分析表明，RNA 裂解途径也存在于人类细胞中，但影响反转录转座子的不同功能。这些结果表明，小 RNA 引导的切割比之前预想的更为广泛。它们对非编码区逆转录转座子的影响揭示了哺乳动物基因调控的重要方面。
In mammals, small RNAs are important players in post-transcriptional gene regulation. While their roles in mRNA destabilization and translational repression are well appreciated, their involvement in endonucleolytic cleavage of target RNAs is poorly understood. Very few microRNAs are known to guide RNA cleavage. Endogenous small interfering RNAs are expected to induce target cleavage, but their target genes remain largely unknown. We report a systematic study of small RNA-mediated endonucleolytic cleavage in mouse through integrative analysis of small RNA and degradome sequencing data without imposing any bias toward known small RNAs. Hundreds of small cleavage-inducing RNAs and their cognate target genes were identified, significantly expanding the repertoire of known small RNA-guided cleavage events. Strikingly, both small RNAs and their target sites demonstrated significant overlap with retrotransposons, providing evidence for the long-standing speculation that retrotransposable elements in mRNAs are leveraged as signals for gene targeting. Furthermore, our analysis showed that the RNA cleavage pathway is also present in human cells but affecting a different repertoire of retrotransposons. These results show that small RNA-guided cleavage is more widespread than previously appreciated. Their impact on retrotransposons in non-coding regions shed light on important aspects of mammalian gene regulation.