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Molecular basis for coordinating transcription termination with noncoding RNA degradation

机译:协调转录终止与非编码RNA降解的分子基础

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The Nrd1-Nab3-Sen1 (NNS) complex is essential for controlling pervasive transcription and generating sn/snoRNAs in S. cerevisiae. The NNS complex terminates transcription of noncoding RNA genes and promotes exosome-dependent processing/degradation of the released transcripts. The Trf4-Air2-Mtr4 (TRAMP) complex polyadenylates NNS target RNAs and favors their degradation. NNS-dependent termination and degradation are coupled, but the mechanism underlying this coupling remains enigmatic. Here we provide structural and functional evidence demonstrating that the same domain of Nrd1p interacts with RNA polymerase II and Trf4p in a mutually exclusive manner, thus defining two alternative forms of the NNS complex, one involved in termination and the other in degradation. We show that the Nrd1-Trf4 interaction is required for optimal exosome activity in vivo and for the stimulation of polyadenylation of NNS targets by TRAMP in vitro. We propose that transcription termination and RNA degradation are coordinated by switching between two alternative partners of the NNS complex.
机译:Nrd1-Nab3-Sen1(NNS)复合体对于控制啤酒酵母中的普遍转录和生成sn / snoRNA至关重要。 NNS复合物终止非编码RNA基因的转录,并促进释放的转录本的外来体依赖性加工/降解。 Trf4-Air2-Mtr4(TRAMP)复合物聚腺苷酸NNS靶向RNA,并有助于其降解。 NNS依赖的终止和降解是耦合的,但是这种耦合的基础机制仍然是个谜。在这里,我们提供结构和功能证据,证明Nrd1p的同一域以互斥方式与RNA聚合酶II和Trf4p相互作用,从而定义了NNS复合物的两种替代形式,一种参与终止,另一种参与降解。我们显示,Nrd1-Trf4相互作用是体内最佳外泌体活性和体外TRAMP刺激NNS目标的多腺苷酸化所必需的。我们建议转录终止和RNA降解通过NNS复杂的两个替代伙伴之间切换来协调。

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