Faculty Opinions recommendation of Pin1 modulates RNA polymerase II activity during the transcription cycle.

2007 ◽  
Author(s):  
Gabriele Varani
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Cycle

scholarly journals Sub1 Globally Regulates RNA Polymerase II C-Terminal Domain Phosphorylation

2010 ◽  
Vol 30 (21) ◽  
pp. 5180-5193 ◽  
Author(s):  
Alicia García ◽  
Emanuel Rosonina ◽  
James L. Manley ◽  
Olga Calvo
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Large Subunit ◽  
Terminal Domain ◽  
Mrna Metabolism ◽  
Genes Encoding ◽  
The One ◽  
Ctd Phosphorylation ◽  
Transcription Cycle

ABSTRACT The transcriptional coactivator Sub1 has been implicated in several aspects of mRNA metabolism in yeast, such as activation of transcription, termination, and 3′-end formation. Here, we present evidence that Sub1 plays a significant role in controlling phosphorylation of the RNA polymerase II large subunit C-terminal domain (CTD). We show that SUB1 genetically interacts with the genes encoding all four known CTD kinases, SRB10, KIN28, BUR1, and CTK1, suggesting that Sub1 acts to influence CTD phosphorylation at more than one step of the transcription cycle. To address this directly, we first used in vitro kinase assays, and we show that, on the one hand, SUB1 deletion increased CTD phosphorylation by Kin28, Bur1, and Ctk1 but, on the other, it decreased CTD phosphorylation by Srb10. Second, chromatin immunoprecipitation assays revealed that SUB1 deletion decreased Srb10 chromatin association on the inducible GAL1 gene but increased Kin28 and Ctk1 chromatin association on actively transcribed genes. Taken together, our data point to multiple roles for Sub1 in the regulation of CTD phosphorylation throughout the transcription cycle.

scholarly journals Functions of the N- and C-Terminal Domains of Human RAP74 in Transcriptional Initiation, Elongation, and Recycling of RNA Polymerase II

1998 ◽  
Vol 18 (4) ◽  
pp. 2130-2142 ◽  
Author(s):  
Lei Lei ◽  
Delin Ren ◽  
Ann Finkelstein ◽  
Zachary F. Burton
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Initiation ◽  
Pol Ii ◽  
Terminal Domain ◽  
Multiple Round ◽  
Major Late Promoter ◽  
Central Loop ◽  
Transcription Cycle ◽  
Terminal Domains

ABSTRACT Transcription factor IIF (TFIIF) cooperates with RNA polymerase II (pol II) during multiple stages of the transcription cycle including preinitiation complex assembly, initiation, elongation, and possibly termination and recycling. Human TFIIF appears to be an α2β2 heterotetramer of RNA polymerase II-associating protein 74- and 30-kDa subunits (RAP74 and RAP30). From inspection of its 517-amino-acid (aa) sequence, the RAP74 subunit appears to comprise separate N- and C-terminal domains connected by a flexible loop. In this study, we present functional data that strongly support this model for RAP74 architecture and further show that the N- and C-terminal domains and the central loop of RAP74 have distinct roles during separate phases of the transcription cycle. The N-terminal domain of RAP74 (minimally aa 1 to 172) is sufficient to deliver pol II into a complex formed on the adenovirus major late promoter with the TATA-binding protein, TFIIB, and RAP30. A more complete N-terminal domain fragment (aa 1 to 217) strongly stimulates both accurate initiation and elongation by pol II. The region of RAP74 between aa 172 and 205 and a subregion between aa 170 and 178 are critical for both accurate initiation and elongation, and mutations in these regions have similar effects on initiation and elongation. Based on these observations, RAP74 appears to have similar functions in initiation and elongation. The central region and the C-terminal domain of RAP74 do not contribute strongly to single-round accurate initiation or elongation stimulation but do stimulate multiple-round transcription in an extract system.

scholarly journals Visualizing the Transcription Cycle of Endogenous RNA Polymerase II in Single Living Cells

2012 ◽  
Vol 102 (3) ◽  
pp. 228a
Author(s):  
Timothy J. Stasevich ◽  
Yoko Hayashi-Takanaka ◽  
Naohito Nozaki ◽  
James G. McNally ◽  
Hiroshi Kimura
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Living Cells ◽  
Single Living Cells ◽  
Single Living ◽  
Transcription Cycle

scholarly journals Multiple Roles for the Ess1 Prolyl Isomerase in the RNA Polymerase II Transcription Cycle

2012 ◽  
Vol 32 (17) ◽  
pp. 3594-3607 ◽  
Author(s):  
Z. Ma ◽  
D. Atencio ◽  
C. Barnes ◽  
H. DeFiglio ◽  
S. D. Hanes
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Multiple Roles ◽  
Prolyl Isomerase ◽  
Rna Polymerase Ii Transcription ◽  
Transcription Cycle

scholarly journals Direct Interactions between the Paf1 Complex and a Cleavage and Polyadenylation Factor Are Revealed by Dissociation of Paf1 from RNA Polymerase II

2008 ◽  
Vol 7 (7) ◽  
pp. 1158-1167 ◽  
Author(s):  
Kristen Nordick ◽  
Matthew G. Hoffman ◽  
Joan L. Betz ◽  
Judith A. Jaehning
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Direct Interaction ◽  
Pol Ii ◽  
Phosphorylated Form ◽  
Cleavage And Polyadenylation ◽  
Paf1 Complex ◽  
Processing Factors ◽  
Polyadenylation Factor ◽  
Transcription Cycle

ABSTRACT The Paf1 complex (Paf1, Ctr9, Cdc73, Rtf1, and Leo1) is normally associated with RNA polymerase II (Pol II) throughout the transcription cycle. However, the loss of either Rtf1 or Cdc73 results in the detachment of the Paf1 complex from Pol II and the chromatin form of actively transcribed genes. Using functionally tagged forms of the Paf1 complex factors, we have determined that, except for the more loosely associated Rtf1, the remaining components stay stably associated with one another in an RNase-resistant complex after dissociation from Pol II and chromatin. The loss of Paf1, Ctr9, or to a lesser extent Cdc73 or Rtf1 results in reduced levels of serine 2 phosphorylation of the Pol II C-terminal domain and in increased read through of the MAK21 polyadenylation site. We found that the cleavage and polyadenylation factor Cft1 requires the Pol II-associated form of the Paf1 complex for full levels of interaction with the serine 5-phosphorylated form of Pol II. When the Paf1 complex is dissociated from Pol II, a direct interaction between Cft1 and the Paf1 complex can be detected. These results are consistent with the Paf1 complex providing a point of contact for recruitment of 3′-end processing factors at an early point in the transcription cycle. The lack of this connection helps to explain the defects in 3′-end formation observed in the absence of Paf1.

scholarly journals Elevated pausing of RNA Polymerase II underlies acquired resistance to ionizing radiation

2021 ◽  
Author(s):  
Kai Yuan ◽  
Honglu Liu ◽  
Chunhong Yu ◽  
Na Zhang ◽  
Yang Meng ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Acquired Resistance ◽  
Cellular Processes ◽  
Genome Wide ◽  
A Genome ◽  
Xenograft Models ◽  
Resistance To Ionizing Radiation ◽  
Transcription Cycle

Abstract As the mainstay modality for many malignancies, ionizing radiation (IR) induces a variety of lesions in genomic DNA, evoking a multipronged DNA damage response to interrupt many cellular processes including transcription. How the global transcription cycle is altered by IR and whether it is contributing to the development of IR-resistance remain unaddressed. Here we report a genome-wide accumulation of paused RNA Polymerase II (RNAPII) after IR exposure. This increased pausing is partially maintained in cells acquired IR-resistance, notably on genes involved in radiation response and cell cycle, often leading to their downregulation. Individual knockdown some of these genes such as TP53 and NEK7 endows IR-sensitive cells with varying degrees of resistance, highlighting a novel link between elevated RNAPII pausing and the acquisition of IR-resistance. Accordingly, tuning-down the RNAPII pausing level by inhibiting CDK7 reverses IR-resistance both in cell culture and xenograft models. Our results suggest that modulation of the transcription cycle is a promising strategy to increase IR-sensitivity and thwart resistance.

scholarly journals Functional Interaction of the Ess1 Prolyl Isomerase with Components of the RNA Polymerase II Initiation and Termination Machineries

2009 ◽  
Vol 29 (11) ◽  
pp. 2925-2934 ◽  
Author(s):  
Shankarling Krishnamurthy ◽  
Mohamed A. Ghazy ◽  
Claire Moore ◽  
Michael Hampsey
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Conformational Changes ◽  
Transcription Initiation ◽  
Serine Phosphorylation ◽  
Initiation Factor ◽  
Prolyl Isomerase ◽  
Pol Ii ◽  
Proline Isomerization ◽  
Transcription Cycle

ABSTRACT The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a reiterated heptad sequence (Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7) that plays a key role in the transcription cycle, coordinating the exchange of transcription and RNA processing factors. The structure of the CTD is flexible and undergoes conformational changes in response to serine phosphorylation and proline isomerization. Here we report that the Ess1 peptidyl prolyl isomerase functionally interacts with the transcription initiation factor TFIIB and with the Ssu72 CTD phosphatase and Pta1 components of the CPF 3′-end processing complex. The ess1 A144T and ess1 H164R mutants, initially described by Hanes and coworkers (Yeast 5:55-72, 1989), accumulate the pSer5 phosphorylated form of Pol II; confer phosphate, galactose, and inositol auxotrophies; and fail to activate PHO5, GAL10, and INO1 reporter genes. These mutants are also defective for transcription termination, but in vitro experiments indicate that this defect is not caused by altering the processing efficiency of the cleavage/polyadenylation machinery. Consistent with a role in initiation and termination, Ess1 associates with the promoter and terminator regions of the PMA1 and PHO5 genes. We propose that Ess1 facilitates pSer5-Pro6 dephosphorylation by generating the CTD structural conformation recognized by the Ssu72 phosphatase and that pSer5 dephosphorylation affects both early and late stages of the transcription cycle.

scholarly journals CTD Tyrosine Phosphorylation Impairs Termination Factor Recruitment to RNA Polymerase II

Science ◽  
2012 ◽  
Vol 336 (6089) ◽  
pp. 1723-1725 ◽  
Author(s):  
Andreas Mayer ◽  
Martin Heidemann ◽  
Michael Lidschreiber ◽  
Amelie Schreieck ◽  
Mai Sun ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Elongation Factor ◽  
Start Site ◽  
Transcription Start ◽  
Termination Factor ◽  
Pol Ii ◽  
Block Factor ◽  
Differential Phosphorylation ◽  
Transcription Cycle

In different phases of the transcription cycle, RNA polymerase (Pol) II recruits various factors via its C-terminal domain (CTD), which consists of conserved heptapeptide repeats with the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. We show that the CTD of transcribing yeast Pol II is phosphorylated at Tyr1, in addition to Ser2, Thr4, Ser5, and Ser7. Tyr1 phosphorylation stimulates binding of elongation factor Spt6 and impairs recruitment of termination factors Nrd1, Pcf11, and Rtt103. Tyr1 phosphorylation levels rise downstream of the transcription start site and decrease before the polyadenylation site, largely excluding termination factors from gene bodies. These results show that CTD modifications trigger and block factor recruitment and lead to an extended CTD code that explains transcription cycle coordination on the basis of differential phosphorylation of Tyr1, Ser2, and Ser5.

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