Xu Zhenyu, Wei Wu, Gagneur Julien, Perocchi Fabiana, Clauder-Münster Sandra, Camblong Jurgi, Guffanti Elisa, Stutz Françoise, Huber Wolfgang, Steinmetz Lars M
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Nature. 2009 Feb 19;457(7232):1033-7. doi: 10.1038/nature07728. Epub 2009 Jan 25.
Genome-wide pervasive transcription has been reported in many eukaryotic organisms, revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non-coding RNAs. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function. Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs or their generation itself. So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome-wide arrangement of these transcripts will be instrumental in understanding their function. Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome-free regions (NFRs) associated with the promoters of other transcripts (mostly protein-coding genes), or from NFRs at the 3' ends of protein-coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals-that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.
在许多真核生物中都报道了全基因组普遍转录现象，这揭示了一种高度交错的转录组组织，其中涉及数百种先前未知的非编码RNA。这些最近鉴定出的转录本要么稳定存在于细胞中（稳定的未注释转录本，SUTs），要么通过RNA监测途径迅速降解（隐蔽的不稳定转录本，CUTs）。普遍转录的一个特征是SUTs和CUTs与先前注释的特征广泛重叠，这引发了关于这些转录本如何产生以及它们是否发挥功能的问题。单基因研究表明，SUTs和CUTs的转录可以是有功能的，其机制涉及产生的RNA或其产生本身。到目前为止，尚未在任何生物体中描述包括SUTs和CUTs在内的完整转录组结构。了解这些转录本的位置和全基因组排列将有助于理解它们的功能。在这里，我们在多种条件、外切体机制突变体和酿酒酵母不同菌株背景的情况下，对这些转录本进行了全面分析。我们表明，SUTs和CUTs在特定位置都显示出不同的分布模式。大多数新鉴定出的转录本起始于与其他转录本（主要是蛋白质编码基因）启动子相关的无核小体区域（NFRs），或起始于蛋白质编码基因3'端的NFRs。同样，所有编码转录本中约有一半起始于与其他转录本启动子相关的NFRs。这些数据改变了我们对基因组转录方式的看法，表明双向性是启动子的固有特征。这种发散和重叠转录本的排列可能为调节信号的局部扩散提供一种机制，即通过转录干扰或组蛋白修饰来耦合相邻基因的转录调控。
