Mechanisms and Functions of the RNA Polymerase II General Transcription Machinery during the Transcription Cycle DOI Creative Commons
Stephen R. Archuleta, James A. Goodrich, Jennifer F. Kugel

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 176 - 176

Published: Feb. 1, 2024

Central to the development and survival of all organisms is regulation gene expression, which begins with process transcription catalyzed by RNA polymerases. During protein-coding genes, general factors (GTFs) work alongside polymerase II (Pol II) assemble preinitiation complex at start site, open promoter DNA, initiate synthesis nascent messenger RNA, transition productive elongation, ultimately terminate transcription. Through these different stages transcription, Pol dynamically phosphorylated C-terminal tail its largest subunit, serving as a control mechanism for elongation signaling/binding platform co-transcriptional factors. The large number core protein participating in fundamental steps add dense layers that contribute complexity temporal spatial expression within any given cell type. system highly conserved across levels eukaryotes; however, most information here will focus on human system. This review walks through various from assembly termination, highlighting functions mechanisms machinery participates each stage.

Language: Английский

Organization and regulation of gene transcription DOI
Patrick Cramer

Nature, Journal Year: 2019, Volume and Issue: 573(7772), P. 45 - 54

Published: Aug. 28, 2019

Language: Английский

Citations

628
Structure of activated transcription complex Pol II–DSIF–PAF–SPT6 DOI
Seychelle M. Vos, Lucas Farnung,

Marc Boehning

et al.

Nature, Journal Year: 2018, Volume and Issue: 560(7720), P. 607 - 612

Published: Aug. 21, 2018

Language: Английский

Citations

408
The genetic changes of Wilms tumour DOI
Taryn D. Treger, Tanzina Chowdhury, Kathy Pritchard‐Jones

et al.

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(4), P. 240 - 251

Published: Jan. 31, 2019

Language: Английский

Citations

225
Causes and consequences of RNA polymerase II stalling during transcript elongation DOI
Melvin Noé González, Daniel Blears, Jesper Q. Svejstrup

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(1), P. 3 - 21

Published: Nov. 18, 2020

Language: Английский

Citations

194
RNA polymerase II speed: a key player in controlling and adapting transcriptome composition DOI Creative Commons
Lisa Muniz, Estelle Nicolas, Didier Trouche

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(15)

Published: July 13, 2021

RNA polymerase II (RNA Pol II) speed or elongation rate, i.e., the number of nucleotides synthesized per unit time, is a major determinant transcriptome composition. It controls co-transcriptional processes such as splicing, polyadenylation, and transcription termination, thus regulating production alternative splice variants, circular RNAs, alternatively polyadenylated transcripts, read-through transcripts. itself regulated in response to intra- extra-cellular stimuli can turn affect composition these stimuli. Evidence points potentially important role modification through regulation for adaptation cells changing environment, pointing function cellular physiology. Analyzing dynamics may therefore be central fully understand physiological processes, development multicellular organisms. Recent findings also raise possibility that deregulation detrimental participate disease progression. Here, we review initial current approaches measure speed, well providing an overview factors controlling which are affected. Finally, discuss cell

Language: Английский

Citations

140
SARS-CoV-2 variants evolve convergent strategies to remodel the host response DOI Creative Commons
Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Benjamin J. Polacco

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4597 - 4614.e26

Published: Sept. 21, 2023

Language: Английский

Citations

73
Paf1C regulates RNA polymerase II progression by modulating elongation rate DOI Creative Commons
Liming Hou, Yating Wang, Yu Liu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(29), P. 14583 - 14592

Published: June 27, 2019

Elongation factor Paf1C regulates several stages of the RNA polymerase II (Pol II) transcription cycle, although it is unclear how modulates Pol distribution and progression in mammalian cells. We found that conditional ablation Paf1 resulted accumulation unphosphorylated Ser5 phosphorylated around promoter-proximal regions within first 20 to 30 kb gene bodies, respectively. did not impact recruitment other key elongation factors, namely, Spt5, Spt6, FACT complex, suggesting function may be mechanistically distinguishable from each these factors. Moreover, loss triggered an increase TSS-proximal nucleosome occupancy, which could impose a considerable barrier past regions. Remarkably, Ser5P coincided with reductions histone H2B ubiquitylation this region. Furthermore, we show nascent species accumulate window, mechanism whereby leads aberrant, prematurely terminated transcripts diminution full-length transcripts. Importantly, results rate defects significant compression. Our findings suggest critical for modulating rates by functioning beyond pause-release step as “accelerator” over specific early body

Language: Английский

Citations

110
Structural Biology of RNA Polymerase II Transcription: 20 Years On DOI

Sara Osman,

Patrick Cramer

Annual Review of Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 36(1), P. 1 - 34

Published: Aug. 21, 2020

Gene transcription by RNA polymerase II (Pol II) is the first step in expression of eukaryotic genome and a focal point for cellular regulation during development, differentiation, responses to environment. Two decades after determination structure Pol II, mechanisms have been elucidated with studies complexes nucleic acids associated proteins. Here we provide an overview nearly 200 available complex structures summarize how these promoter-dependent initiation, promoter-proximal pausing release into active elongation, that uses navigate obstacles such as nucleosomes DNA lesions. We predict future will focus on interconnected chromatin transitions, processing, repair.

Language: Английский

Citations

104
SETD5 Regulates Chromatin Methylation State and Preserves Global Transcriptional Fidelity during Brain Development and Neuronal Wiring DOI Creative Commons
Alessandro Sessa, Luca Fagnocchi, Giuseppina Mastrototaro

et al.

Neuron, Journal Year: 2019, Volume and Issue: 104(2), P. 271 - 289.e13

Published: Sept. 9, 2019

Language: Английский

Citations

92
Two distinct mechanisms of RNA polymerase II elongation stimulation in vivo DOI Creative Commons
Kristina Žumer,

Kerstin C. Maier,

Lucas Farnung

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(15), P. 3096 - 3109.e8

Published: June 18, 2021

Transcription by RNA polymerase II (RNA Pol II) relies on the elongation factors PAF1 complex (PAF), RTF1, and SPT6. Here, we use rapid factor depletion multi-omics analysis to investigate how these influence activity in human cells. Whereas of PAF subunits CTR9 has little effect cellular synthesis, RTF1 or SPT6 strongly compromises activity, albeit fundamentally different ways. decreases velocity, whereas impairs progression through nucleosomes. These results show that distinct stimulate either velocity chromatin vivo. Further provides evidence for two barriers early elongation: promoter-proximal pause site +1 nucleosome. It emerges first barrier enables loading are required overcome second subsequent transcription.

Language: Английский

Citations

92