Nuclear stability and transcriptional directionality separate functionally distinct RNA species

Nuclear stability and transcriptional directionality separate functionally distinct RNA species
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DOI:
10.1038/ncomms6336
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发表时间:
2014-11-01
影响因子:
16.6
通讯作者:
Sandelin, Albin
Sandelin, Albin
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Andersson, Robin;Andersen, Peter Refsing;Sandelin, Albin

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哺乳动物基因组普遍被转录,产生了一个复杂的转录组,在组成和细胞丰度上具有高度的可变性。尽管最近的研究已经发现了数千种新的长链非编码(lnc) RNA,并证明了蛋白质编码(pc)基因产生的复杂转录库,但在区分功能性RNA和虚假转录事件方面进展有限。这部分是由于目前的RNA分类,这通常是基于技术而不是生化标准。在这里,我们设计了一种策略来系统地分类人类RNA,根据它们对核糖核溶解RNA外泌体复合物的敏感性和它们转录起始的性质。这些方法在正确分类带注释的转录本(包括已知功能的lncrna)方面出奇地有效。该方法还可以识别隐藏在绝大多数不稳定转录本中的未表征的稳定lncrna。该方法的预测能力有望简化已知和新型rna的功能分析。
Mammalian genomes are pervasively transcribed, yielding a complex transcriptome with high variability in composition and cellular abundance. Although recent efforts have identified thousands of new long non-coding (lnc) RNAs and demonstrated a complex transcriptional repertoire produced by protein-coding (pc) genes, limited progress has been made in distinguishing functional RNA from spurious transcription events. This is partly due to present RNA classification, which is typically based on technical rather than biochemical criteria. Here we devise a strategy to systematically categorize human RNAs by their sensitivity to the ribonucleolytic RNA exosome complex and by the nature of their transcription initiation. These measures are surprisingly effective at correctly classifying annotated transcripts, including lncRNAs of known function. The approach also identifies uncharacterized stable lncRNAs, hidden among a vast majority of unstable transcripts. The predictive power of the approach promises to streamline the functional analysis of known and novel RNAs.