title: Structural mimicry in transcription regulation of human RNA polymerase II by the DNA helicase RECQL5.
abstract: RECQL5 is a member of the highly conserved RecQ family of DNA helicases involved in DNA repair. RECQL5 interacts with RNA polymerase II (Pol II) and inhibits transcription of protein-encoding genes by an unknown mechanism. We show that RECQL5 contacts the Rpb1 jaw domain of Pol II at a site that overlaps with the binding site for the transcription elongation factor TFIIS. Our cryo-EM structure of elongating Pol II arrested in complex with RECQL5 shows that the RECQL5 helicase domain is positioned to sterically block elongation. The crystal structure of the RECQL5 KIX domain reveals similarities with TFIIS, and binding of RECQL5 to Pol II interferes with the ability of TFIIS to promote transcriptional read-through in vitro. Together, our findings reveal a dual mode of transcriptional repression by RECQL5 that includes structural mimicry of the Pol II-TFIIS interaction.
authors.affiliation: Biophysics Graduate Group, University of California, Berkeley, California, USA.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Kassube
authors.forename: Martin
authors.initials: M
authors.lastname: Jinek
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.forename: Susan
authors.initials: S
authors.lastname: Tsutakawa
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D053484:RecQ Helicases / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D061805:Transcription Elongation, Genetic; D035602:Transcriptional Elongation Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure
chemical_list: C506732:RECQL5 protein, human; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D012319:RNA Polymerase II; C410949:RNA polymerase II largest subunit; D053484:RecQ Helicases