Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Science. 2012 Nov 2;338(6107):671-5. doi: 10.1126/science.1224350. Epub 2012 Sep 27.
Eukaryotic genomes are extensively transcribed, forming both messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). ncRNAs made by RNA polymerase II often initiate from bidirectional promoters (nucleosome-depleted chromatin) that synthesize mRNA and ncRNA in opposite directions. We demonstrate that, by adopting a gene-loop conformation, actively transcribed mRNA encoding genes restrict divergent transcription of ncRNAs. Because gene-loop formation depends on a protein factor (Ssu72) that coassociates with both the promoter and the terminator, the inactivation of Ssu72 leads to increased synthesis of promoter-associated divergent ncRNAs, referred to as Ssu72-restricted transcripts (SRTs). Similarly, inactivation of individual gene loops by gene mutation enhances SRT synthesis. We demonstrate that gene-loop conformation enforces transcriptional directionality on otherwise bidirectional promoters.
真核基因组广泛转录，形成信使 RNA（mRNA）和非编码 RNA（ncRNA）。由 RNA 聚合酶 II 产生的 ncRNA 通常起始于双向启动子（核小体缺失染色质），该启动子以相反的方向合成 mRNA 和 ncRNA。我们证明，通过采用基因环构象，活跃转录的 mRNA 编码基因限制了 ncRNA 的发散转录。由于基因环形成取决于一种与启动子和终止子都结合的蛋白质因子（Ssu72），因此 Ssu72 的失活导致与启动子相关的发散 ncRNA 的合成增加，称为 Ssu72 限制转录物（SRT）。同样，通过基因突变使单个基因环失活会增强 SRT 的合成。我们证明，基因环构象在其他双向启动子上强制转录方向。
