title: Molecular basis for coordinating transcription termination with noncoding RNA degradation.
abstract: 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.
authors: Centre de Génétique Moléculaire, CNRS UPR3404, 91190 Gif sur Yvette, France.
authors: Agnieszka
authors: A
authors: Tudek
authors: Centre de Génétique Moléculaire, CNRS UPR3404, 91190 Gif sur Yvette, France. Electronic address: porrua@ijm.univ-paris-diderot.fr.
authors: Odil
authors: O
authors: Porrua
authors: CEITEC-Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 62500, Czech Republic.
authors: Tomasz
authors: T
authors: Kabzinski
authors: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
authors: Michael
authors: M
authors: Lidschreiber
authors: CEITEC-Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 62500, Czech Republic.
authors: Karel
authors: K
authors: Kubicek
authors: CEITEC-Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 62500, Czech Republic.
authors: Andrea
authors: A
authors: Fortova
authors: Centre de Génétique Moléculaire, CNRS UPR3404, 91190 Gif sur Yvette, France.
authors: François
authors: F
authors: Lacroute
authors: CEITEC-Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 62500, Czech Republic.
authors: Stepanka
authors: S
authors: Vanacova
authors: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
authors: Patrick
authors: P
authors: Cramer
authors: CEITEC-Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 62500, Czech Republic. Electronic address: richard.stefl@ceitec.muni.cz.
authors: Richard
authors: R
authors: Stefl
authors: Centre de Génétique Moléculaire, CNRS UPR3404, 91190 Gif sur Yvette, France. Electronic address: libri.domenico@ijm.univ-paris-diderot.fr.
authors: Domenico
authors: D
authors: Libri
mesh_terms: D001665:Binding Sites; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D026723:Polyadenylation; D012319:RNA Polymerase II / Q000378:metabolism*; D020871:RNA Stability; D012331:RNA, Fungal / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D061806:Transcription Termination, Genetic
chemical_list: C491211:NRD1 protein, S cerevisiae; D012331:RNA, Fungal; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; D004259:DNA-Directed DNA Polymerase; C487545:PAP2 protein, S cerevisiae