A single flexible RNAPII-CTD integrates many different transcriptional programs

Aristizabal, Maria J.; Kobor, Michæl S.

doi:10.1080/21541264.2016.1163451

Cited by 3 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pol II is a large multi-unit protein complex, with its largest subunit RPB1 as the core of Pol II transcriptional machinery. The CTD of RPB1 contains various numbers of highly conserved heptad peptide (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) repeat, ranging from 26 in budding yeast and 29 in fission yeast to 34 in Arabidopsis and 52 in human [ 20 , 25 , 26 , 27 , 28 , 29 , 30 ]. Each of the seven amino acids in the repeat may undergo different modifications (e.g., S/T/Y phosphorylation, S glycosylation, and P isomerization), and each repeat may have a different posttranslational modification pattern [ 31 ].…”

Section: Control Of Transcription During the Cell Cyclementioning

confidence: 99%

Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control: Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

Zheng

2022

Cells

View full text Add to dashboard Cite

Cell cycle control is vital for cell proliferation in all eukaryotic organisms. The entire cell cycle can be conceptually separated into four distinct phases, Gap 1 (G1), DNA synthesis (S), G2, and mitosis (M), which progress sequentially. The precise control of transcription, in particular, at the G1 to S and G2 to M transitions, is crucial for the synthesis of many phase-specific proteins, to ensure orderly progression throughout the cell cycle. This mini-review highlights highly conserved transcriptional regulators that are shared in budding yeast (Saccharomyces cerevisiae), Arabidopsis thaliana model plant, and humans, which have been separated for more than a billion years of evolution. These include structurally and/or functionally conserved regulators cyclin-dependent kinases (CDKs), RNA polymerase II C-terminal domain (CTD) phosphatases, and the classical versus shortcut models of Pol II transcriptional control. A few of CDKs and CTD phosphatases counteract to control the Pol II CTD Ser phosphorylation codes and are considered critical regulators of Pol II transcriptional process from initiation to elongation and termination. The functions of plant-unique CDKs and CTD phosphatases in relation to cell division are also briefly summarized. Future studies towards testing a cooperative transcriptional mechanism, which is proposed here and involves sequence-specific transcription factors and the shortcut model of Pol II CTD code modulation, across the three eukaryotic kingdoms will reveal how individual organisms achieve the most productive, large-scale transcription of phase-specific genes required for orderly progression throughout the entire cell cycle.

show abstract

Section: Control Of Transcription During the Cell Cyclementioning

confidence: 99%

Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control: Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

Zheng

2022

Cells

View full text Add to dashboard Cite

show abstract

“…In our prior work, we have found that Rho family GTPases, including ROP2/4 in the Arabidopsis model plants and Cdc42 in fission yeast, modulate the phosphorylation status of Ser2 and Ser5 in the C-terminal domain (CTD) of RPB1, the largest subunit of Pol II, effecting gene expression and the control of cell shape, cell size and cell number [8]. The Pol II CTD contains various number of the heptad peptide (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) repeat, ranging from 29 repeats in fission yeast and 34 in Arabidopsis to 52 in humans [9][10][11][12]. Dynamic post-translational modifications of these seven residues in each repeat, in particular phosphorylation of Ser2 and Ser5, constitutes a very complex pattern called the "CTD code", which is critical for completing key steps of the transcription cycle [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…The Pol II CTD contains various number of the heptad peptide (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) repeat, ranging from 29 repeats in fission yeast and 34 in Arabidopsis to 52 in humans [9][10][11][12]. Dynamic post-translational modifications of these seven residues in each repeat, in particular phosphorylation of Ser2 and Ser5, constitutes a very complex pattern called the "CTD code", which is critical for completing key steps of the transcription cycle [9][10][11][12]. The CTD code is created and maintained by several CTD kinases and CTD phosphatases.…”

Section: Introductionmentioning

confidence: 99%

Modulation of the Pol II CTD Phosphorylation Code by Rac1 and Cdc42 Small GTPases in Cultured Human Cancer Cells and Its Implication for Developing a Synthetic-Lethal Cancer Therapy

Zhang¹,

Zhong²,

Sauane³

et al. 2020

Cells

View full text Add to dashboard Cite

Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD Ser phosphatases RPAP2 and FCP1, they both decreased the level of CTD kinases CDK7 and CDK13. In addition, the protein degradation inhibitor MG132 reversed the effect of THZ1, a CDK7 inhibitor which could decrease the cell number and amount of CDK7 and CDK13, accompanied by a reduction in the level of CTD Ser2 and Ser5 phosphorylation and DOCK4 and DOCK9 (the activators for Rac1 and Cdc42, respectively). Conversely, treatments of Torin1 or serum deprivation, both of which promote protein degradation, could enhance the effect of THZ1, indicating the involvement of protein degradation in controlling CDK7 and CDK13. Our results support an evolutionarily conserved signaling shortcut model linking Rho GTPases to Pol II transcription across three kingdoms, Fungi, Plantae and Animalia, and could lead to the development of a potential synthetic-lethal strategy in controlling cancer cell proliferation or death.

show abstract

“…The C-terminal domain (CTD) of RPB1, the largest subunit of Pol II, contains a certain number of both highly conserved heptad peptide (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) repeats and slightly variant repeats, ranging from a total of 29 repeats in fission yeast, 34 in Arabidopsis to 52 in humans. [3][4][5][6][7][8] Each of the amino acid residues in the repeats can be modified posttranslationally, such as phosphorylation of Tyr1, Ser2, Thr4, Ser5 and Ser7, isomerization at Pro3 and Pro6 and acetylation at Thr4. Thus, various modifications on the large number of the repeats theoretically would result in very complex combinations, and because of their importance in transcriptional control, these modification patterns on the CTD repeats have bene collectively dubbed the "CTD code".…”

Section: Introductionmentioning

confidence: 99%

“…Thus, various modifications on the large number of the repeats theoretically would result in very complex combinations, and because of their importance in transcriptional control, these modification patterns on the CTD repeats have bene collectively dubbed the "CTD code". [3][4][5][6][7][8] Accumulating evidence shows that dynamic modulation of the CTD code in Pol II along genes is essential for completing key steps of transcription, by recruiting the CTD-associated proteins to the transcribing Pol II, including several CTD kinases and CTD phosphatases. The role Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Ras and Rho GTPase regulation of Pol II transcription: A shortcut model revisited

Zheng

2017

Transcription

View full text Add to dashboard Cite

Transcriptional control is critical in relaying signals mediated by Ras and Rho family small GTPases to effect gene expression. In the classical model, signaling components such as MAP kinase target sequence-specific transcription factors, which in turn recruit RNA polymerase (Pol) II holoenzyme to the promoter and activate transcription. Findings in recent years have led to the proposal of a shortcut model in which the Mediator components of the Pol II holoenzyme are regulated by signaling pathways. A very recent finding shows that an evolutionarily conserved Rho GTPase signaling pathway can directly modulate the Pol II C-terminal domain (CTD) phosphorylation by inhibiting the CTD phosphatase in yeast and Arabidopsis. This shortcut model allows direct targeting of the Pol II CTD code and thus has an advantage over the classical model in bringing about rapid, large-scale changes in gene expression.

show abstract

A single flexible RNAPII-CTD integrates many different transcriptional programs

Cited by 3 publications

References 30 publications

Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control: Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control: Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

Modulation of the Pol II CTD Phosphorylation Code by Rac1 and Cdc42 Small GTPases in Cultured Human Cancer Cells and Its Implication for Developing a Synthetic-Lethal Cancer Therapy

Ras and Rho GTPase regulation of Pol II transcription: A shortcut model revisited

Contact Info

Product

Resources

About