Transcriptome Surveillance by Selective Termination of Noncoding RNA Synthesis
Transcriptome Surveillance by Selective Termination of Noncoding RNA Synthesis
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DOI：
10.1016/j.cell.2013.10.024
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发表时间：
2013-11-21
期刊：
影响因子：
64.5
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
--
作者：
Schulz, Daniel;Schwalb, Bjoern;Cramer, Patrick
真核生物基因组的普遍转录在很大程度上源于合成mRNA和趋异非编码RNA（ncRNA）的双向启动子。在这里，我们表明，ncRNA转录在酵母S。酿酒酵母是全球性的限制，早期终止依赖于必要的RNA结合因子Nrd1。Nrd1从细胞核中缺失导致1，526个Nrd1未终止的转录物（NUT），这些转录物来自核小体缺失区（NDRs），可以通过反义抑制和转录干扰来解除mRNA合成的调控。转录组范围内的Nrd1结合图谱显示，不同的NUT在大多数启动子和反义NUT在大多数30个区域的基因。Nrd1和它的伙伴Nab3优先结合RNA基序，这些基序在mRNA中耗尽，在ncRNA和一些mRNA中富集，这些mRNA的合成受转录衰减控制。这些结果定义了一个全球性的转录组监视机制，选择性地终止ncRNA的合成，提供启动子的方向性和抑制反义转录。
Pervasive transcription of eukaryotic genomes stems to a large extent from bidirectional promoters that synthesize mRNA and divergent noncoding RNA (ncRNA). Here, we show that ncRNA transcription in the yeast S. cerevisiae is globally restricted by early termination that relies on the essential RNA-binding factor Nrd1. Depletion of Nrd1 from the nucleus results in 1,526 Nrd1-unterminated transcripts (NUTs) that originate from nucleosome-depleted regions (NDRs) and can deregulate mRNA synthesis by antisense repression and transcription interference. Transcriptome-wide Nrd1-binding maps reveal divergent NUTs at most promoters and antisense NUTs in most 30 regions of genes. Nrd1 and its partner Nab3 preferentially bind RNA motifs that are depleted in mRNAs and enriched in ncRNAs and some mRNAs whose synthesis is controlled by transcription attenuation. These results define a global mechanism for transcriptome surveillance that selectively terminates ncRNA synthesis to provide promoter directionality and to suppress antisense transcription.