The RNA Polymerase II C-terminal Domain-interacting Domain of Yeast Nrd1 Contributes to the Choice of Termination Pathway and Couples to RNA Processing by the Nuclear Exosome
The RNA Polymerase II C-terminal Domain-interacting Domain of Yeast Nrd1 Contributes to the Choice of Termination Pathway and Couples to RNA Processing by the Nuclear Exosome
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DOI：
10.1074/jbc.m113.508267
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发表时间：
2013-12-20
影响因子：
4.8
通讯作者：
Kim, Minkyu
中科院分区：
文献类型：
--
作者：
Heo, Dong-hyuk;Yoo, Inhea;Kim, Minkyu
背景资料：酵母RNA聚合酶II（RNApII）的不同终止途径采用识别RNApII C末端结构域（CTD）不同磷酸形式的蛋白质（Nrd 1和Rtt 103）。结果：Nrd 1 CTD结合特异性的改变显著影响RNApII的终止。结论：RNApII CTD和终止因子之间的差异相互作用在选择终止途径中至关重要。重要性：Nrd 1的CTD相互作用结构域（CTD interacting domain）是核外泌体对RNA的终止和加工的偶联结构域，RNA聚合酶II（RNApII）的C末端结构域（CTD）相互作用结构域（CID）蛋白参与两种不同的RNApII终止途径，并识别不同磷酸化形式的CTD。为了研究不同的CTD-CID相互作用在选择终止途径中的作用，我们通过结构域交换改变了Nrd 1的CTD结合特异性。具有来自Rtt 103的CID的Nrd 1（Nrd 1（CIDRtt 103））在许多基因处引起通读转录，但也可以在多个Nrd 1/Nab 3结合位点和Ser（P）-2 CTD共存的情况下触发终止。因此，CTD-CID相互作用靶向特定的终止复合物，以帮助选择RNApII终止途径。Nrd 1与CTD和新生转录物的相互作用有助于Nrd 1复合物的有效终止。令人惊讶的是，用来自Rtt 103的CID替换Nrd 1 CID减少了与Rrp 6/Trf 4的结合，并且由Nrd 1（CIDRtt 103）终止的RNA转录物主要由核心外泌体加工。因此，Nrd 1 CID不仅将Ser（P）-5 CTD与终止偶联，而且与核外泌体的RNA加工偶联。
Background: Distinct termination pathways for yeast RNA polymerase II (RNApII) employ proteins (Nrd1 and Rtt103) recognizing different phospho-forms of the RNApII C-terminal domain (CTD). Results: Alteration of CTD-binding specificity of Nrd1 significantly affects RNApII termination. Conclusion: Differential interaction between RNApII CTD and termination factors is crucial in choosing a termination pathway. Significance: CTD-interacting domain of Nrd1 couples termination and RNA processing by the nuclear exosome.The RNA polymerase II (RNApII) C-terminal domain (CTD)-interacting domain (CID) proteins are involved in two distinct RNApII termination pathways and recognize different phosphorylated forms of CTD. To investigate the role of differential CTD-CID interactions in the choice of termination pathway, we altered the CTD-binding specificity of Nrd1 by domain swapping. Nrd1 with the CID from Rtt103 (Nrd1(CIDRtt103)) causes read-through transcription at many genes, but can also trigger termination where multiple Nrd1/Nab3-binding sites and the Ser(P)-2 CTD co-exist. Therefore, CTD-CID interactions target specific termination complexes to help choose an RNApII termination pathway. Interactions of Nrd1 with both CTD and nascent transcripts contribute to efficient termination by the Nrd1 complex. Surprisingly, replacing the Nrd1 CID with that from Rtt103 reduces binding to Rrp6/Trf4, and RNA transcripts terminated by Nrd1(CIDRtt103) are predominantly processed by core exosome. Thus, the Nrd1 CID couples Ser(P)-5 CTD not only to termination, but also to RNA processing by the nuclear exosome.