Structure of the complete elongation complex of RNA polymerase II with basal factors

Ehara, Haruhiko; Yokoyama, Takeshi; Shigematsu, Hideki; Yokoyama, Shigeyuki; Shirouzu, Mikako; Sekine, S.

doi:10.1126/science.aan8552

Cited by 166 publications

(217 citation statements)

References 45 publications

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“…By guiding NT DNA along the optimal path, a regulator could support pause-free transcription. Third, holding the NT strand in place could modulate DNA reannealing behind RNAP, in turn controlling translocation, R-loop formation, and the trajectory of upstream DNA duplex that interacts with Spt5 (Crickard et al, 2016;Ehara et al, 2017) and perhaps other accessory factors. While relative contributions of NTD interactions with the DNA and RNAP may vary, the available data suggest that many if not all NusG-like proteins are able to restrict the mobility of the transcription bubble to modify RNAP into a pause-and arrest-resistant state.…”

Section: Diverse Roles Of the Nt Dna In Rna Synthesismentioning

confidence: 99%

“…Subsequent structural analyses and molecular modeling revealed that the NTD‐RNAP interactions are broadly conserved among bacterial, yeast, mammalian and archaeal factors (Klein et al ., ; Martinez‐Rucobo et al ., ; Turtola and Belogurov, ; Yakhnin et al ., ; Bernecky et al ., ; Ehara et al ., ) and that the clamp opens a paused bacterial EC (Weixlbaumer et al ., ). Together, these data supported a ubiquitous antipausing mechanism shared by all NusG homologs.…”

Section: Introductionmentioning

confidence: 99%

“…(Guo et al, 2015) Spt5 with the upstream DNA. A recent structure of yeast Komagataella pastoris EC revealed that Spt4/5 encircles one turn of the duplex DNA behind the RNAP in a 'DNA exit tunnel' (Ehara et al, 2017). In this work, we set out to investigate the contribution of DNA interactions to RfaH effects on the EC.…”

Section: Introductionmentioning

confidence: 99%

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Locking the nontemplate DNA to control transcription

Nedialkov

Svetlov

Belogurov

et al. 2018

Molecular Microbiology

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Universally conserved NusG/Spt5 factors reduce RNA polymerase pausing and arrest. In a widely accepted model, these proteins bridge the RNA polymerase clamp and lobe domains across the DNA channel, inhibiting the clamp opening to promote pause-free RNA synthesis. However, recent structures of paused transcription elongation complexes show that the clamp does not open and suggest alternative mechanisms of antipausing. Among these mechanisms, direct contacts of NusG/Spt5 proteins with the nontemplate DNA in the transcription bubble have been proposed to prevent unproductive DNA conformations and thus inhibit arrest. We used Escherichia coli RfaH, whose interactions with DNA are best characterized, to test this idea. We report that RfaH stabilizes the upstream edge of the transcription bubble, favoring forward translocation, and protects the upstream duplex DNA from exonuclease cleavage. Modeling suggests that RfaH loops the nontemplate DNA around its surface and restricts the upstream DNA duplex mobility. Strikingly, we show that RfaH-induced DNA protection and antipausing activity can be mimicked by shortening the nontemplate strand in elongation complexes assembled on synthetic scaffolds. We propose that remodeling of the nontemplate DNA controls recruitment of regulatory factors and R-loop formation during transcription elongation across all life.

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Section: Diverse Roles Of the Nt Dna In Rna Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Locking the nontemplate DNA to control transcription

Nedialkov

Svetlov

Belogurov

et al. 2018

Molecular Microbiology

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“…Most of the textbooks in molecular biology describe in detail how general transcription factors, including TBP, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH, co-operatively work to recruit RNA pol II appropriately onto the TSSs [3]. Recently, structure of the eukaryotic RNA pol II complex, containing elongation factors, Spt4/5, Elf1, and TFIIS, has been revealed [4]. The entire transcription reaction system from initiation to termination on DNA template will be elucidated in the near future.…”

Section: Transcriptional Controlling System In Eukaryotic Cellsmentioning

confidence: 99%

Introductory Chapter: Current Studies in Transcriptional Control System; Toward the Establishment of Therapies against Human Diseases

Uchiumi¹

2018

Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects

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“…The superhelically wrapped DNA shares the geometry, diameter, pitch, and writhe of the eukaryotic nucleosomal superhelix, and specific protein-DNA contacts that stabilize archaeal chromatin are conserved in eukaryotes (Luger et al, 1997;Mattiroli et al, 2017;Bhattacharyya et al, 2018). The eukaryotic nuclear RNA polymerases (RNAPs) and the archaeal RNAP thus regularly encounter -and must overcome -nearly identical histone-based barriers to transcription elongation (Kireeva et al, 2005;Teves et al, 2014;Ehara et al, 2017;Mattiroli et al, 2017;Kujirai et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin

Sanders

Lammers

Marshall

et al. 2019

Molecular Microbiology

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Summary RNA polymerase must surmount translocation barriers for continued transcription. In Eukarya and most Archaea, DNA‐bound histone proteins represent the most common and troublesome barrier to transcription elongation. Eukaryotes encode a plethora of chromatin‐remodeling complexes, histone‐modification enzymes and transcription elongation factors to aid transcription through nucleosomes, while archaea seemingly lack machinery to remodel/modify histone‐based chromatin and thus must rely on elongation factors to accelerate transcription through chromatin‐barriers. TFS (TFIIS in Eukarya) and the Spt4–Spt5 complex are universally encoded in archaeal genomes, and here we demonstrate that both elongation factors, via different mechanisms, can accelerate transcription through archaeal histone‐based chromatin. Histone proteins in Thermococcus kodakarensis are sufficiently abundant to completely wrap all genomic DNA, resulting in a consistent protein barrier to transcription elongation. TFS‐enhanced cleavage of RNAs in backtracked transcription complexes reactivates stalled RNAPs and dramatically accelerates transcription through histone‐barriers, while Spt4–Spt5 changes to clamp‐domain dynamics play a lesser‐role in stabilizing transcription. Repeated attempts to delete TFS, Spt4 and Spt5 from the T. kodakarensis genome were not successful, and the essentiality of both conserved transcription elongation factors suggests that both conserved elongation factors play important roles in transcription regulation in vivo, including mechanisms to accelerate transcription through downstream protein barriers.

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Structure of the complete elongation complex of RNA polymerase II with basal factors

Cited by 166 publications

References 45 publications

Locking the nontemplate DNA to control transcription

Locking the nontemplate DNA to control transcription

Introductory Chapter: Current Studies in Transcriptional Control System; Toward the Establishment of Therapies against Human Diseases

TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin

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