title: The conserved protein Seb1 drives transcription termination by binding RNA polymerase II and nascent RNA.
abstract: Termination of RNA polymerase II (Pol II) transcription is an important step in the transcription cycle, which involves the dislodgement of polymerase from DNA, leading to release of a functional transcript. Recent studies have identified the key players required for this process and showed that a common feature of these proteins is a conserved domain that interacts with the phosphorylated C-terminus of Pol II (CTD-interacting domain, CID). However, the mechanism by which transcription termination is achieved is not understood. Using genome-wide methods, here we show that the fission yeast CID-protein Seb1 is essential for termination of protein-coding and non-coding genes through interaction with S2-phosphorylated Pol II and nascent RNA. Furthermore, we present the crystal structures of the Seb1 CTD- and RNA-binding modules. Unexpectedly, the latter reveals an intertwined two-domain arrangement of a canonical RRM and second domain. These results provide important insights into the mechanism underlying eukaryotic transcription termination.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Sina
authors.initials: S
authors.lastname: Wittmann
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Max
authors.initials: M
authors.lastname: Renner
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Beth R
authors.initials: BR
authors.lastname: Watts
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Adams
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Miles
authors.initials: M
authors.lastname: Huseyin
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Baejen
authors.affiliation: Diamond Light Source Ltd, Harwell Science &Innovation Campus, Didcot OX11 0DE, UK.
authors.forename: Kamel
authors.identifier: 0000-0003-3506-6045
authors.initials: K
authors.lastname: El Omari
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kilchert
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Heo
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Tea
authors.initials: T
authors.lastname: Kecman
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.|Diamond Light Source Ltd, Harwell Science &Innovation Campus, Didcot OX11 0DE, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grimes
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Lidia
authors.identifier: 0000-0002-1244-8772
authors.initials: L
authors.lastname: Vasiljeva
mesh_terms: D001483:Base Sequence; D002470:Cell Survival; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D005800:Genes, Fungal; D008954:Models, Biological; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding; D000072417:Protein Domains; D012319:RNA Polymerase II / Q000378:metabolism*; D012331:RNA, Fungal / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D061806:Transcription Termination, Genetic
chemical_list: D009687:Nuclear Proteins; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C000627950:Seb1 protein, S pombe; D012319:RNA Polymerase II