Functional classification of long non-coding RNAs by k-mer content.

Functional classification of long non-coding RNAs by k-mer content.
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DOI:
10.1038/s41588-018-0207-8
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发表时间:
2018-10
期刊:
影响因子:
30.8
通讯作者:
Calabrese JM
Calabrese JM
中科院分区:
生物学1区
文献类型:
--
作者:
Kirk JM;Kim SO;Inoue K;Smola MJ;Lee DM;Schertzer MD;Wooten JS;Baker AR;Sprague D;Collins DW;Horning CR;Wang S;Chen Q;Weeks KM;Mucha PJ;Calabrese JM

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大多数长链非编码RNA(lncRNA)的功能尚不清楚。与蛋白质相反,具有相似功能的lncRNA通常缺乏线性序列同源性;因此,在一种lncRNA中鉴定功能很少告知在其他lncRNA中鉴定功能。我们开发了一种序列比较方法来解构lncRNA中的线性序列关系,并基于称为kmers的短基序的丰度来评估相似性。我们发现,尽管缺乏线性同源性,但具有相关功能的lncRNA通常具有相似的kmer谱,并且kmer谱与蛋白质与lncRNA的结合及其亚细胞定位相关。使用一种新的检测方法来定量Xist样调控潜力,我们直接证明了进化无关的lncRNA可以通过相关序列基序的不同空间排列编码类似的功能。基于Kmer的分类是检测lncRNA中序列和功能之间的重复关系的有力方法。
The functions of most long non-coding RNAs (lncRNAs) are unknown. In contrast to proteins, lncRNAs with similar functions often lack linear sequence homology; thus, the identification of function in one lncRNA rarely informs the identification of function in others. We developed a sequence comparison method to deconstruct linear sequence relationships in lncRNAs and evaluate similarity based on the abundance of short motifs called kmers. We found that lncRNAs of related function often had similar kmer profiles despite lacking linear homology, and that kmer profiles correlated with protein binding to lncRNAs and with their subcellular localization. Using a novel assay to quantify Xist-like regulatory potential, we directly demonstrated that evolutionarily unrelated lncRNAs can encode similar function through different spatial arrangements of related sequence motifs. Kmer-based classification is a powerful approach to detect recurrent relationships between sequence and function in lncRNAs.
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