Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Cell Rep. 2021 Jan 19;34(3):108640. doi: 10.1016/j.celrep.2020.108640.
In multicellular eukaryotes, RNA polymerase (Pol) II pauses transcription ~30-50 bp after initiation. While the budding yeast Saccharomyces has its transcription mechanisms mostly conserved with other eukaryotes, it appears to lack this fundamental promoter-proximal pausing. However, we now report that nearly all yeast genes, including constitutive and inducible genes, manifest two distinct transcriptional stall sites that are brought on by acute environmental signaling (e.g., peroxide stress). Pol II first stalls at the pre-initiation stage before promoter clearance, but after DNA melting and factor acquisition, and may involve inhibited dephosphorylation. The second stall occurs at the +2 nucleosome. It acquires most, but not all, elongation factor interactions. Its regulation may include Bur1/Spt4/5. Our results suggest that a double Pol II stall is a mechanism to downregulate essentially all genes in concert.
在多细胞真核生物中，RNA 聚合酶（Pol）II 在起始后约 30-50 bp 处暂停转录。虽然芽殖酵母酿酒酵母的转录机制与其他真核生物大多保守，但它似乎缺乏这种基本的启动子近端暂停。然而，我们现在报告说，几乎所有的酵母基因，包括组成型和诱导型基因，都表现出两种不同的转录停滞位点，这些位点是由急性环境信号（如过氧化物应激）引起的。Pol II 首先在启动子清除之前在起始前阶段停滞，但在 DNA 熔化和因子获取之后，可能涉及抑制去磷酸化。第二个停顿发生在+2 核小体处。它获得了大部分，但不是全部，伸长因子相互作用。其调节可能包括 Bur1/Spt4/5。我们的结果表明，双 Pol II 停顿是一种协同下调几乎所有基因的机制。
