Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs.
Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs.
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DOI：
10.1186/s13059-016-0880-9
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发表时间：
2016-02-02
期刊：
影响因子：
12.3
通讯作者：
Garber M
中科院分区：
文献类型：
--
作者：
Chen J;Shishkin AA;Zhu X;Kadri S;Maza I;Guttman M;Hanna JH;Regev A;Garber M
转录组测序的最新进展使得在许多物种中发现了数千种长链非编码rna （lncrna）。尽管一些lncrna已被证明在多种生物过程中发挥重要作用，但大多数lncrna的功能和机制尚不清楚。转录组测序和lncrna的功能表征之间存在两个重大障碍：从从头重建的转录组中识别真正的非编码基因，并优先考虑数百个由此产生的假定lncrna进行下游实验研究。我们提出了slnky，一个lncRNA发现工具，从rna测序数据中产生一组高质量的lncRNA，并进一步使用进化约束来优先考虑可能具有重要功能的lncRNA。我们的自动过滤管道与人工管理工作相当，比以前发表的计算方法更敏感。此外，我们开发了一个敏感的lncRNA位点比对管道，并提出了与分析序列和转录物进化相关的新进化指标。我们的分析揭示了进化选择以几种不同的模式起作用，并揭示了两类显著的基因间lncrna：一类对RNA序列表现出强烈的纯化选择，另一类约束仅限于转录本的调控而不是序列。我们的研究结果强调lncrna不是一类同质的分子，而是具有不同生物学机制和/或作用的多种功能类的混合物。我们新颖的lncrna比较方法揭示了数万个当前注释的转录本中233个受限的lncrna，我们通过灵巧的进化浏览器提供了这些转录本。本文的在线版本（doi:10.1186/s13059-016-0880-9）包含补充材料，仅供授权用户使用。
Recent advances in transcriptome sequencing have enabled the discovery of thousands of long non-coding RNAs (lncRNAs) across many species. Though several lncRNAs have been shown to play important roles in diverse biological processes, the functions and mechanisms of most lncRNAs remain unknown. Two significant obstacles lie between transcriptome sequencing and functional characterization of lncRNAs: identifying truly non-coding genes from de novo reconstructed transcriptomes, and prioritizing the hundreds of resulting putative lncRNAs for downstream experimental interrogation. We present slncky, a lncRNA discovery tool that produces a high-quality set of lncRNAs from RNA-sequencing data and further uses evolutionary constraint to prioritize lncRNAs that are likely to be functionally important. Our automated filtering pipeline is comparable to manual curation efforts and more sensitive than previously published computational approaches. Furthermore, we developed a sensitive alignment pipeline for aligning lncRNA loci and propose new evolutionary metrics relevant for analyzing sequence and transcript evolution. Our analysis reveals that evolutionary selection acts in several distinct patterns, and uncovers two notable classes of intergenic lncRNAs: one showing strong purifying selection on RNA sequence and another where constraint is restricted to the regulation but not the sequence of the transcript. Our results highlight that lncRNAs are not a homogenous class of molecules but rather a mixture of multiple functional classes with distinct biological mechanism and/or roles. Our novel comparative methods for lncRNAs reveals 233 constrained lncRNAs out of tens of thousands of currently annotated transcripts, which we make available through the slncky Evolution Browser. The online version of this article (doi:10.1186/s13059-016-0880-9) contains supplementary material, which is available to authorized users.