Mol Biol Evol：北京大学李川昀课题组发表RNA编辑位点新文章

近日，molecular biology and Evolution杂志发表北京大学分子医学研究所李川昀课题组与台湾长庚大学谭贤明教授合作的研究论文，论文指出研究人员发现并命名一类含有RNA编辑位点的piRNA分子，揭示RNA编辑可能对piRNA生成起到功能性的调控作用，在灵长类中首次建立了RNA编辑与piRNA调控的功能联系。文章题为“Selectively Constrained RNA Editing Regulation Crosstalks with piRNA Biogenesis in Primates”。北京大学分子医学研究所杨欣壮、陈加余同学为本文并列第一作者。研究受到国家自然科学基金、国家973项目等经费支持。

RNA编辑可引起基因组与其编码的转录组在特定位点的序列差异。近年来，数以万计的RNA编辑位点被报道，而这些调控多数(>99%)位于不编码蛋白质的基因组区域。这些非编码性的编辑调控是否具有生物学功能，是该领域悬而未解的难题。李川昀课题组前期运用猴的人类近缘优势，获得了精确的猴全编辑组，并从分子演化角度首次证明非编码区的RNA编辑在理论上具有功能性(PLoS genetics, 2014)。然而，它们具体通过怎样的调控途径来实现其功能呢?

在本文中，作者针对猴多组织、多个体、多调控层次开展了系统的组学研究，发现了一类由发生RNA编辑的长转录本前体经剪切而形成的pirna分子，并将其命名为epiRNA(editing-bearing PIWI-interacting RNA)。研究进一步发现RNA编辑对piRNA生成具有显著的促进作用，而这些发生在epiRNA上的RNA编辑事件正经历着显著的负向自然选择作用(Purifying Selection)，提示在人类、猴等灵长类动物中，与piRNA调控的相互作用可能是RNA编辑发挥生物学功能的主要途径之一。本研究首次建立了RNA编辑与piRNA调控之间的功能联系，为针对这两类调控的机制研究提供了新视角。

原文链接：

Selectively Constrained RNA Editing Regulation Crosstalks with piRNA BioGENEsis in Primates

原文摘要：

While millions of RNA editing events have been reported to modify hereditary information across the primate transcriptome, evidence for their functional significance remains largely elusive, particularly for the vast majority of editing sites in non-coding regions. Here we report a new mechanism for the functionality of RNA editing – a crosstalk with piRNA biogenesis. Exploiting rhesus macaque as an emerging model organism closely related to human, in combination with extensive genome and transcriptome sequencing in seven tissues of the same animal, we deciphered accurate RNA editome across both long transcripts and the piRNA species. Superimposing and comparing these two distinct RNA editome profiles revealed 4,170 editing-bearing piRNA variants, or epiRNAs, that primarily derived from edited long transcripts. These epiRNAs represent distinct entities that evidence an intersection between RNA editing regulations and piRNA biogenesis. Population genetics analyses in a macaque population of 31 independent animals further demonstrated that the epiRNAs-associated RNA editing are maintained by purifying selection, lending support to the functional significance of this crosstalk in rhesus macaque. Correspondingly, these findings are consistent in human, supporting the conservation of this mechanism during the primate evolution. Overall, our study reports the earliest lines of evidence for a crosstalk between selectively-constrained RNA editing regulation and piRNA biogenesis, and further illustrates that such an interaction may contribute substantially to the diversification of the piRNA repertoire in primates.

doi: 10.1093/molbev/msv183

作者：李川昀