Widespread bidirectional promoters are the major source of cryptic transcripts in yeast
Widespread bidirectional promoters are the major source of cryptic transcripts in yeast
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DOI：
10.1038/nature07747
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发表时间：
2009-02-19
期刊：
影响因子：
64.8
通讯作者：
Jacquier, Alain
中科院分区：
文献类型：
--
作者：
Neil, Helen;Malabat, Christophe;Jacquier, Alain
真核生物中普遍存在着广泛的隐性转录(1-4)，但其全球水平、起源机制及其功能意义尚不清楚。隐蔽的不稳定转录本(CUTS)最近被描述为酿酒酵母中RNA聚合酶II转录本的主要类别(5)。这些转录本在合成后立即通过Nrd1-外切体-TRAMP复合体(6，7)的作用而被降解。虽然已经详细分析了切割降解的机制，但核苷酸分辨率和切割的流行率在全基因组中的分布尚不清楚。在这里，我们报道了第一个酵母切割的高分辨率基因组图谱，揭示了一类潜在的功能切割和真核生物启动子的内在双向性质。采用适合于深度测序的3‘长SAGE(基因表达序列分析)方法对切割后高度浓缩的RNA组分进行了分析。由此得到的详细的基因组图谱显示，它们来自极其广泛和非常明确的转录单位，而不是非特定的转录噪音。此外，切割的转录主要发生在无核小体区域，其中大部分对应于真基因的启动子区域。一些切割开始于信使RNA的上游，并与它们的59端重叠。我们对糖酵解基因的研究以及最近文献(8-11)的结果表明，这种并行转录可能与调控机制有关。我们的数据显示，许多新的削减具有这种潜在的监管作用。然而，大多数已鉴定的切割对应于与基因启动子区域不同的转录本，这表明它们代表了许多甚至可能是大多数启动子中存在的不同转录的副产物。因此，真核生物的启动子区域本质上是双向的，这一基本属性逃脱了先前的分析，因为在大多数情况下，分歧转录会产生短暂的不稳定转录，目前处于非常低的稳定水平。
Pervasive and hidden transcription is widespread in eukaryotes(1-4), but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts ( CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae(5). These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1 - exosome - TRAMP complexes(6,7). Although CUT degradation mechanisms have been analysed in detail, the genome- wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown. Here we report the first high- resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters. An RNA fraction highly enriched in CUTs was analysed by a 3 ' Long- SAGE ( serial analysis of gene expression) approach adapted to deep sequencing. The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise. Moreover, the transcription of CUTs predominantly arises within nucleosome- free regions, most of which correspond to promoter regions of bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap their 59 end. Our study of glycolysis genes, as well as recent results from the literature(8-11), indicate that such concurrent transcription is potentially associated with regulatory mechanisms. Our data reveal numerous new CUTs with such a potential regulatory role. However, most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by- products of divergent transcription occurring at many and possibly most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional, a fundamental property that escaped previous analyses because in most cases divergent transcription generates short- lived unstable transcripts present at very low steady- state levels.