title: The crystal structure of the 5΄ functional domain of the transcription riboregulator 7SK.
abstract: In vertebrates, the 7SK RNA forms the scaffold of a complex, which regulates transcription pausing of RNA-polymerase II. By binding to the HEXIM protein, the complex comprising proteins LARP7 and MePCE captures the positive transcription elongation factor P-TEFb and prevents phosphorylation of pausing factors. The HEXIM-binding site embedded in the 5΄-hairpin of 7SK (HP1) encompasses a short signature sequence, a GAUC repeat framed by single-stranded uridines. The present crystal structure of HP1 shows a remarkably straight helical stack involving several unexpected triples formed at a central region. Surprisingly, two uridines of the signature sequence make triple interactions in the major groove of the (GAUC)2. The third uridine is turned outwards or inward, wedging between the other uridines, thus filling the major groove. A molecular dynamics simulation indicates that these two conformations of the signature sequence represent stable alternatives. Analyses of the interaction with the HEXIM protein confirm the importance of the triple interactions at the signature sequence. Altogether, the present structural analysis of 7SK HP1 highlights an original mechanism of swapping bases, which could represent a possible '7SK signature' and provides new insight into the functional importance of the plasticity of RNA.
authors.affiliation: Biotechnologie et signalisation cellulaire, CNRS UMR 7242, Ecole Supérieure de Biotechnologie de Strasbourg, F-67412 Illkirch, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Martinez-Zapien
authors.affiliation: Synchrotron SOLEIL, L'Orme des Merisiers, F-91190 Gif-sur-Yvette, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Legrand
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwen
authors.affiliation: Department of functional genomics, CNRS UMR 8197, Institut de Biologie de l΄Ecole Normale Supérieure F-75005 Paris, France.|Department of functional genomics, INSERM-U1024, Institut de Biologie de l΄Ecole Normale Supérieure F-75005 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Proux
authors.affiliation: University Chemical Laboratories, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Tristan
authors.initials: T
authors.lastname: Cragnolini
authors.affiliation: Laboratoire de Biochimie Théorique, IBPC, CNRS UPR 9080, Université Sorbonne Paris Cite, Paris Diderot, 75005 Paris, France.
authors.forename: Samuela
authors.initials: S
authors.lastname: Pasquali
authors.affiliation: Department of functional genomics, CNRS UMR 8197, Institut de Biologie de l΄Ecole Normale Supérieure F-75005 Paris, France.|Department of functional genomics, INSERM-U1024, Institut de Biologie de l΄Ecole Normale Supérieure F-75005 Paris, France.|Sorbonne Universités UPMC, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, F-29688, Roscoff cedex, France.|CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, CS 90074, F-29688, Roscoff cedex, France.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Dock-Bregeon
mesh_terms: D000225:Adenine / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D009690:Nucleic Acid Conformation; D062085:RNA, Long Noncoding / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors; D014529:Uridine / Q000737:chemistry
chemical_list: C476123:HEXIM1 protein, human; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C000610089:long non-coding RNA 7SK, human; D000225:Adenine; D014529:Uridine