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Book The Functional Significance of the Carboxyl terminal Domain of RNA Polymerase IIa o

Download or read book The Functional Significance of the Carboxyl terminal Domain of RNA Polymerase IIa o written by Paul James Laybourn and published by . This book was released on 1989 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book A Functional Analysis of the RNA Polymerase II Large Subunit Carboxy terminal Domain

Download or read book A Functional Analysis of the RNA Polymerase II Large Subunit Carboxy terminal Domain written by Rob Chapman and published by . This book was released on 2002 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book The Role of RNA Polymerase II Phosphorylation in the Early Stages of Transcription

Download or read book The Role of RNA Polymerase II Phosphorylation in the Early Stages of Transcription written by Jonathan Donald Chesnut and published by . This book was released on 1994 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book The C terminal Domain of RNA Polymerase II

Download or read book The C terminal Domain of RNA Polymerase II written by Anton Yuryev and published by . This book was released on 1995 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Role of the RNA Polymerase II C terminal Domain in Transcription Termination and Function of Spt5 in 3 RNA processing Factor Recruitment

Download or read book Role of the RNA Polymerase II C terminal Domain in Transcription Termination and Function of Spt5 in 3 RNA processing Factor Recruitment written by Amelie Erna Schreieck and published by . This book was released on 2013 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Phosphatases and Prolyl isomerase in the Regulation of the C terminal Domain of Eukaryotic RNA Polymerase II

Download or read book Phosphatases and Prolyl isomerase in the Regulation of the C terminal Domain of Eukaryotic RNA Polymerase II written by Mengmeng Zhang and published by . This book was released on 2012 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: In eukaryotes, the first step of interpreting the genetic information is the transcription of DNA into RNA. For protein-coding genes, such transcription is carried out by RNA polymerase II. A special domain of RNA polymerase II, called the C-terminal domain (CTD), functions as a master controller for the transcription process by providing a platform to recruit regulatory proteins to nascent mRNA (Chapter 1-2). The modifications and conformational states of the CTD, termed the 'CTD code', represent a critical regulatory checkpoint for transcription. The CTD, found only in eukaryotes, consists of 26--52 tandem heptapeptide repeats with the consensus sequence, Tyr1Ser2Pro3Thr4Ser5Pro6Ser--. Phosphorylation of the serines and prolyl isomerization of the prolines represent two major regulatory mechanisms of the CTD. Interestingly, the phosphorylation sites are typically close to prolines, thus the conformation of the adjacent proline could impact the specificity of the corresponding kinases and phosphatases. Understanding how those modifying enzymes recognize and regulate the CTD is important for expanding our knowledge on the transcription regulation and deciphering the 'CTD code'. During my PhD study, I studied the function of CTD phosphatases and prolyl isomerase in the CTD regulation using Scp1, Ssu72 and Pin1 as model regulators. Scp1 and Ssu72 are both Ser5 phosphatases. However, Ssu72 is an essential protein and regulates the global transcription while Scp1 epigenetically silences the expression of specific neuronal genes. Pin1 is a highly conserved phosphorylation-specific prolyl isomerase that recognizes the phospho-Ser/Thr-Pro motif within the CTD as one of its primary substrates in vivo. Among these enzymes, Scp1 is the focal point of this dissertation, as it was studied from different angles, such as enzymatic mechanism (Chapter 3 describes the capture of phospho-aspartyl intermediate of Scp1 as a direct evidence for the proposed two-step mechanism), specific inhibition (Chapter 4 describes the identification and characterization of the first specific inhibitor of Scp1), and its non-active-site contact with the CTD (Chapter 5 describes the structural basis of this contact). These studies are of great importance towards understanding the molecular mechanism of the dephosphorylation process of the CTD by Scp1.

Book RNA Polymerase II Carboxy terminal Domain Phosphatase

Download or read book RNA Polymerase II Carboxy terminal Domain Phosphatase written by Michael S. Kobor and published by . This book was released on 2001 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The form of RNA polymerase II (RNAPII) that binds preferentially to promoters is not extensively phosphorylated on the carboxy-terminal heptapeptide repeat domain (CTD) of its largest subunit. The CTD becomes phosphorylated during or shortly after initiation and elongating RNAPII generally has a phosphorylated CTD. Prior to or following transcriptional termination, dephosphorylation of the CTD presumably must occur to regenerate the hypophosphorylated form of RNAPII that is capable of reinitiating transcription. This thesis examines the function of the CTD phosphatase Fcp1p in the yeast 'Saccharomyces cerevisiae'. In chapter 2, it is shown that Fcp1 is an unusual eukaryotic protein phosphatase that is required for dephosphorylation of the CTD 'in vivo ' and for transcription by RNAPII 'in vivo'. These results suggest that Fcp1p is the founding member of a new class of protein phosphatases and acts as a general transcription factor 'in vivo'. In chapter 3, affinity chromatography is used to study the binding of Fcp1p to TFIIB and the RAP74 subunit of TFIIF. Fcp1p binds in a similar way to both of these factors. RAP74 and TFIIB have a short region of homology and amino acid changes in this region affect the binding to Fcp1p. The genes encoding RAP74 and Fcp1p interact 'in vivo'. Fcp1p can activate transcription when artificially tethered to a promoter and this effect is largely dependent on binding to RAP74. In chapter 4, it is shown that yeast strains with mutations in ' fcp1' grow much worse when the gene encoding the major CTD kinase Kin28p is also mutated. In contrast, inactivation of another CTD kinase encoded by the 'SRB10' gene suppresses the temperature-sensitivity and the sensitivity to certain cell cycle checkpoint inducing drugs of ' fcp1' mutant strains. These results therefore suggest that Fcp1p and Srb10p have opposing roles 'in vivo'. In chapter 5, analysis of the phosphorylation state of the CTD reveals that reduced Fcp1p activity results in a increased amount of the largest subunit of RNAPII but this subunit is not incorporated into functional enzyme and is largely degraded at a higher temperature.

Book Structural Heterogeneity in the RNA Polymerase II C Terminal Domain

Download or read book Structural Heterogeneity in the RNA Polymerase II C Terminal Domain written by Bede Portz and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA polymerase II contains a repetitive and intrinsically disordered C-Terminal Domain (CTD) composed of heptad repeats of the consensus sequence YSPTSPS. The CTD can be heavily phosphorylated and serves as a scaffold, interacting with factors involved in transcription initiation, elongation, termination, RNA processing and chromatin modification. Despite its role as a nexus of eukaryotic gene regulation, the structure of the CTD and the structural implications of CTD phosphorylation, are poorly understood. Additionally, there is an increasing awareness of the importance of intrinsically disordered proteins (IDPs) that function without adopting a stably folded structure. Here I present a biophysical and biochemical interrogation of the structure of the full-length CTD of D. melanogaster, which I conclude is a compact random coil. I find that the repetitive CTD is structurally heterogeneous as evidenced by a discontinuous pattern of cutting in limited proteolysis assays. Small Angle X-Ray scattering (SAXS) is a method ideally suited for the structural interrogation of large IDPs and can be employed to measure the size of a protein and to monitor structural changes in response to post-translational modification. Using SAXS I determined that phosphorylation by the kinase P-TEFb caused an increase in CTD radius and stiffness. Limited proteolysis of the phosphorylated CTD showed these gross structural changes are accompanied by increased protease accessibility and an alteration in relative protease accessibility across the length of the CTD.Additionally, we show that the human CTD is also structurally heterogeneous and able to substitute for the Drosophila melanogaster CTD in supporting the development of flies to adulthood. These finding implicate conserved structural organization, not a precise array of heptad motifs, as important to CTD function.The CTD is attached to the catalytic core of Pol II via a linker. I show that this linker is more compact than the CTD repeats and serves as an independent structural unit. The phosphorylated linker-CTD remains flexible relative to the phosphorylated CTD alone. Together, these results support a mechanism by which phosphorylation reduces the conformational entropy of the CTD, generating a more binding competent dock for CTD:protein interactions, with the linker region maintaining the ability of CTD bound factors to sample the 3-dimensional space which may be required for RNA processing and histone modification.The data described herein represent the most thorough structural characterization to date of the full length CTD on the global and local scales, examining both the overall size and local structural organization of the CTD. These studies establish the Drosophila CTD as an attractive model for the biophysical, biochemical and genetic interrogation of the structure and function of the CTD from a developmentally complex organism.

Book Post translational Modification of the C terminal Domain of RNA Polymerase II

Download or read book Post translational Modification of the C terminal Domain of RNA Polymerase II written by Joshua Edward Mayfield and published by . This book was released on 2017 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA polymerase II is a highly regulated protein complex that transcribes all protein coding mRNA and many non-coding RNAs. A key mechanism that facilitates its activity is post-translational modification of the carboxyl-terminal domain of RNA polymerase II (CTD). This unstructured domain is conserved throughout eukaryotes and composed of repeats of the consensus amino acid heptad Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. This domain acts as a platform for the recruitment of transcriptional regulators that specifically recognize post-translational modification states of the CTD. The majority of our understanding of CTD modification comes from the use of phospho-specific antibodies, which provide identity and abundance information but give only low-resolution information for how these marks co-exist and interact at the molecular level. During my graduate work I sought to utilize the tools of chemical biology to investigate CTD modification in high resolution. Using a combination of chemical tools, analytical chemistry, and molecular biology I studied CTD modification in extremely high resolution. This work reveals the existence of interactions between CTD modifications, the influence of CTD sequence divergence on modification events, and presents initial data to support a role for previously encoded modifications to direct subsequent modification events

Book Molecular Biology of RNA

Download or read book Molecular Biology of RNA written by Masayori Inouye and published by . This book was released on 1987 with total page 472 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Biology of RNA: New Perspectives provides an overview of the developments in RNA research as well as the approaches, strategies, and methodologies used. Most of the contributing authors in the present volume participated in the Fifth Stony Brook Symposium entitled ""New Perspectives on the Molecular Biology of RNA"" in May 1986. The text is organized into six parts. Part I contains papers dealing with RNA as an enzyme. Part II presents studies on RNA splicing. Part III examines RNA viruses while Part IV focuses on the role of RNA in DNA replication. Part V is devoted to the structure ...

Book RNA Polymerase II Carboxy terminal Domain Phosphatase

Download or read book RNA Polymerase II Carboxy terminal Domain Phosphatase written by and published by . This book was released on 2001 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Transcription and Splicing

Download or read book Transcription and Splicing written by B. D. Hames and published by Oxford University Press, USA. This book was released on 1988 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives a co-ordinated review of our present knowledge of eukaryotic RNA synthesis.