title: Exosome Cofactors Connect Transcription Termination to RNA Processing by Guiding Terminated Transcripts to the Appropriate Exonuclease within the Nuclear Exosome.
abstract: 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.
authors.affiliation: From the Department of Cellular and Molecular Pharmacology, University of California and California Institute for Quantitative Biosciences, San Francisco, California 94158.
authors.forename: Kyumin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, United Kingdom.
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Heo
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 08826, Korea, and.
authors.forename: Iktae
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 08826, Korea, and Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Jeong-Yong
authors.initials: JY
authors.lastname: Suh
authors.affiliation: From the Department of Cellular and Molecular Pharmacology, University of California and California Institute for Quantitative Biosciences, San Francisco, California 94158, minkyu.kim@ucsf.edu.
authors.forename: Minkyu
authors.identifier: 0000-0001-9317-1658
authors.initials: M
authors.lastname: Kim
mesh_terms: D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D005092:Exonucleases / Q000378:metabolism*; D055354:Exosomes / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D012331:RNA, Fungal / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C531213:Mpp6 protein, S cerevisiae; C491211:NRD1 protein, S cerevisiae; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D004259:DNA-Directed DNA Polymerase; C487545:PAP2 protein, S cerevisiae; D005092:Exonucleases
keywords: RNA processing; exosome complex; nuclear RNA; transcription termination; yeast two-hybrid