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Termination of non-coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD-mimicking region in Sen1.
The EMBO Journal ( IF 11.4 ) Pub Date : 2020-02-28 , DOI: 10.15252/embj.2019101548 Zhong Han 1, 2 , Olga Jasnovidova 3 , Nouhou Haidara 1, 2 , Agnieszka Tudek 1 , Karel Kubicek 3 , Domenico Libri 1 , Richard Stefl 3 , Odil Porrua 1
The EMBO Journal ( IF 11.4 ) Pub Date : 2020-02-28 , DOI: 10.15252/embj.2019101548 Zhong Han 1, 2 , Olga Jasnovidova 3 , Nouhou Haidara 1, 2 , Agnieszka Tudek 1 , Karel Kubicek 3 , Domenico Libri 1 , Richard Stefl 3 , Odil Porrua 1
Affiliation
Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a threat to proper gene expression that needs to be controlled. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here, we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy-terminal domain (CTD) of RNA polymerase II, and structurally characterize its recognition by the CTD-interacting domain of Nrd1, an RNA-binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-dependent termination strictly requires CTD recognition by the N-terminal domain of Sen1. We provide evidence that the Sen1-CTD interaction does not promote initial Sen1 recruitment, but rather enhances Sen1 capacity to induce the release of paused RNAPII from the DNA. Our results shed light on the network of protein-protein interactions that control termination of non-coding transcription by Sen1.
中文翻译:
酵母中非编码转录的终止依赖于RNA Pol II CTD相互作用域和Sen1中的CTD模拟区域。
普遍转录是一种普遍现象,导致产生大量没有明显功能的非编码RNA(ncRNA)。普遍的转录对需要控制的适当基因表达构成威胁。在酵母中,高度保守的解旋酶Sen1通过诱导非编码转录终止来限制普遍的转录。但是,人们尚不清楚Sen1在ncRNA处的特定功能的机制。在这里,我们在Sen1的内在无序区域中识别出一个基序,该基序模仿RNA聚合酶II的磷酸化羧基末端结构域(CTD),并通过Nrd1的CTD相互作用域结构化表征其识别,Nrd1是一种结合RNA的结合蛋白ncRNA中的特定序列。此外,我们表明,Sen1依赖性终止严格要求通过Sen1的N端域进行CTD识别。我们提供的证据表明,Sen1-CTD相互作用不会促进最初的Sen1募集,而是增强Sen1诱导从DNA释放暂停的RNAPII的能力。我们的结果阐明了控制Sen1非编码转录终止的蛋白相互作用的网络。
更新日期:2020-04-01
中文翻译:
酵母中非编码转录的终止依赖于RNA Pol II CTD相互作用域和Sen1中的CTD模拟区域。
普遍转录是一种普遍现象,导致产生大量没有明显功能的非编码RNA(ncRNA)。普遍的转录对需要控制的适当基因表达构成威胁。在酵母中,高度保守的解旋酶Sen1通过诱导非编码转录终止来限制普遍的转录。但是,人们尚不清楚Sen1在ncRNA处的特定功能的机制。在这里,我们在Sen1的内在无序区域中识别出一个基序,该基序模仿RNA聚合酶II的磷酸化羧基末端结构域(CTD),并通过Nrd1的CTD相互作用域结构化表征其识别,Nrd1是一种结合RNA的结合蛋白ncRNA中的特定序列。此外,我们表明,Sen1依赖性终止严格要求通过Sen1的N端域进行CTD识别。我们提供的证据表明,Sen1-CTD相互作用不会促进最初的Sen1募集,而是增强Sen1诱导从DNA释放暂停的RNAPII的能力。我们的结果阐明了控制Sen1非编码转录终止的蛋白相互作用的网络。