Kim Kyumin, Heo Dong-Hyuk, Kim Iktae, Suh Jeong-Yong, Kim Minkyu
From the Department of Cellular and Molecular Pharmacology, University of California and California Institute for Quantitative Biosciences, San Francisco, California 94158.
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, United Kingdom.
J Biol Chem. 2016 Jun 17;291(25):13229-42. doi: 10.1074/jbc.M116.715771. Epub 2016 Apr 13.
The yeast Nrd1 interacts with the C-terminal domain (CTD) of RNA polymerase II (RNApII) through its CTD-interacting domain (CID) and also associates with the nuclear exosome, thereby acting as both a transcription termination and RNA processing factor. Previously, we found that the Nrd1 CID is required to recruit the nuclear exosome to the Nrd1 complex, but it was not clear which exosome subunits were contacted. Here, we show that two nuclear exosome cofactors, Mpp6 and Trf4, directly and competitively interact with the Nrd1 CID and differentially regulate the association of Nrd1 with two catalytic subunits of the exosome. Importantly, Mpp6 promotes the processing of Nrd1-terminated transcripts preferentially by Dis3, whereas Trf4 leads to Rrp6-dependent processing. This suggests that Mpp6 and Trf4 may play a role in choosing a particular RNA processing route for Nrd1-terminated transcripts within the exosome by guiding the transcripts to the appropriate exonuclease.
酵母Nrd1通过其CTD相互作用结构域（CID）与RNA聚合酶II（RNApII）的C末端结构域（CTD）相互作用，并且还与核外泌体相关联，因此它既是转录终止因子又是RNA加工因子。此前，我们发现Nrd1 CID是将核外泌体招募到Nrd1复合物所必需的，但尚不清楚与哪些外泌体亚基发生了接触。在此，我们表明两个核外泌体辅因子Mpp6和Trf4直接且竞争性地与Nrd1 CID相互作用，并差异调节Nrd1与外泌体的两个催化亚基的结合。重要的是，Mpp6优先促进Dis3对Nrd1终止转录本的加工，而Trf4导致Rrp6依赖性加工。这表明Mpp6和Trf4可能通过将转录本引导至合适的核酸外切酶，在为外泌体内Nrd1终止的转录本选择特定的RNA加工途径中发挥作用。
