title: RNA polymerase-induced remodelling of NusA produces a pause enhancement complex.
abstract: Pausing during transcription elongation is a fundamental activity in all kingdoms of life. In bacteria, the essential protein NusA modulates transcriptional pausing, but its mechanism of action has remained enigmatic. By combining structural and functional studies we show that a helical rearrangement induced in NusA upon interaction with RNA polymerase is the key to its modulatory function. This conformational change leads to an allosteric re-positioning of conserved basic residues that could enable their interaction with an RNA pause hairpin that forms in the exit channel of the polymerase. This weak interaction would stabilize the paused complex and increases the duration of the transcriptional pause. Allosteric spatial re-positioning of regulatory elements may represent a general approach used across all taxa for modulation of transcription and protein-RNA interactions.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.affiliation: Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mobli
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Keller
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia Peter.Lewis@newcastle.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lewis
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D010445:Peptide Elongation Factors; D012329:RNA, Bacterial; D014157:Transcription Factors; D012321:DNA-Directed RNA Polymerases