Chinese Academy of Sciences Key Laboratory of Computational Biology, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Society Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Rep. 2017 Jan 31;7:41669. doi: 10.1038/srep41669.
Recently, long non-coding RNAs (lncRNAs) have emerged as an important class of molecules involved in many cellular processes. One of their primary functions is to shape epigenetic landscape through interactions with chromatin modifying proteins. However, mechanisms contributing to the specificity of such interactions remain poorly understood. Here we took the human and mouse lncRNAs that were experimentally determined to have physical interactions with Polycomb repressive complex 2 (PRC2), and systematically investigated the sequence features of these lncRNAs by developing a new computational pipeline for sequences composition analysis, in which each sequence is considered as a series of transitions between adjacent nucleotides. Through that, PRC2-binding lncRNAs were found to be associated with a set of distinctive and evolutionarily conserved sequence features, which can be utilized to distinguish them from the others with considerable accuracy. We further identified fragments of PRC2-binding lncRNAs that are enriched with these sequence features, and found they show strong PRC2-binding signals and are more highly conserved across species than the other parts, implying their functional importance.
最近,长非编码 RNA(lncRNA)作为参与许多细胞过程的一类重要分子而出现。它们的主要功能之一是通过与染色质修饰蛋白的相互作用来塑造表观遗传景观。然而,导致这种相互作用特异性的机制仍知之甚少。在这里,我们选择了实验确定与多梳抑制复合物 2(PRC2)具有物理相互作用的人类和小鼠 lncRNA,并通过开发一种新的序列组成分析计算管道,系统地研究了这些 lncRNA 的序列特征,其中每个序列被视为相邻核苷酸之间的一系列跃迁。通过这种方式,发现 PRC2 结合 lncRNA 与一组独特且进化上保守的序列特征相关联,这些特征可用于以相当高的准确性将其与其他 lncRNA 区分开来。我们进一步鉴定了富含这些序列特征的 PRC2 结合 lncRNA 片段,并发现它们表现出强烈的 PRC2 结合信号,并且在物种间比其他部分更保守,这表明它们具有功能重要性。