Global Mapping of Human RNA-RNA Interactions
Global Mapping of Human RNA-RNA Interactions
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DOI：
10.1016/j.molcel.2016.04.030
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发表时间：
2016-05-19
期刊：
影响因子：
16
通讯作者：
Blencowe, Benjamin J.
中科院分区：
文献类型：
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作者：
Sharma, Eesha;Sterne-Weiler, Tim;Blencowe, Benjamin J.
人类基因组的大部分被转录成非编码（nc）RNA，这些RNA缺乏已知的生物学功能或仅被部分表征。许多特征性的ncRNA通过与靶RNA序列的碱基配对来指导其生物活性，包括在RNA加工、修饰、周转和翻译中的关键作用。为了定义ncRNA的作用，我们开发了一种方法，该方法能够在体内交联的RNA-RNA双链体的全球规模映射，“相互作用RNA的连接，然后进行高通量测序”（LIGR-seq）。在人类细胞中应用这种方法揭示了涉及所有主要类别的ncRNA和mRNA的RNA-RNA相互作用的显着景观。LIGR-seq数据揭示了小核仁（sno）RNA和mRNA之间的意想不到的相互作用，包括涉及孤儿C/D盒snoRNA，SNORD 83 B的相互作用，其控制其靶mRNA的稳态水平。因此，LIGR-seq代表了一种强有力的方法，用于阐明通过碱基配对相互作用起作用的无数未表征RNA的功能。
The majority of the human genome is transcribed into non-coding (nc) RNAs that lack known biological functions or else are only partially characterized. Numerous characterized ncRNAs function via base pairing with target RNA sequences to direct their biological activities, which include critical roles in RNA processing, modification, turnover, and translation. To define roles for ncRNAs, we have developed a method enabling the global-scale mapping of RNA-RNA duplexes crosslinked in vivo, "LIGation of interacting RNA followed by high-throughput sequencing'' (LIGR-seq). Applying this method in human cells reveals a remarkable landscape of RNA-RNA interactions involving all major classes of ncRNA and mRNA. LIGR-seq data reveal unexpected interactions between small nucleolar (sno) RNAs and mRNAs, including those involving the orphan C/D box snoRNA, SNORD83B, that control steady-state levels of its target mRNAs. LIGR-seq thus represents a powerful approach for illuminating the functions of the myriad of uncharacterized RNAs that act via base-pairing interactions.