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Author: Anthony Chun-yin Chiu
Publisher:
ISBN:
Category :
Languages : en
Pages : 221
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Book Description
Transcription is one of the most fundamental processes in cells, governing the conversion of genetic information to RNA. Numerous regulatory mechanisms function to ensure that desired transcripts are being expressed. Promoters transcribe divergently, producing low-abundant upstream antisense RNAs (uaRNAs) in addition to a stable downstream RNAs. Thus, a central question is what mechanisms are sense RNAs more stable compared to most transcription events. It is proposed that an asymmetric distribution of Ul snRNP binding sites and polyadenylation site (PAS) motifs known as the UI-PAS axis regulates early termination of RNA Polymerase II. Here, we generated a conditional knockout of the essential RNA exosome subunit, Exosc3, in mouse embryonic stem cells. Removal of Exosc3 resulted in stabilization of polyadenylated uaRNAs, enhancer RNAs and long noncoding RNAs. In addition, promoter proximal pausing increased modestly upon Exosc3 removal. Interestingly, a large class of polyadenylated short transcripts in the sense direction terminate within the first intron, similar to premature termination observed upon Ul inhibition. Further investigation of these prematurely termination sites revealed they are found at the edges of stable nucleosome free regions demarcated by CpG islands and are suppressed by U1 snRNP. Interestingly, promoter-proximal Pol II pausing consists of two processes: TSS-proximal and +1 stable nucleosome pausing. Genes associated with premature termination have increased +1 stable nucleosome pausing, association of chromatin remodelers and are more sensitive to inhibition by flavopiridol or a Myc inhibitor. Additionally, the nuclear poly(A) binding protein, Pabpnl, promotes degradation of polyadenylated uaRNAs. Most Pabpnl sensitive uaRNAs are also Exosc3 substrates, and sensitivity to Pabpnl inhibition inversely correlates with the proximity of the termination site to the TSS. Interestingly, at uaRNAs and sense RNAs, Pabpnl -sensitive PAS termination events also occur near the first stable nucleosome, similar to Exosc3-sensitive PAS termination events, suggesting that Pabpnl collaborates with Exosc3 to regulate stability of polyadenylated transcripts. Hence, this supports a model whereby Ul snRNP, +1 stable nucleosomes and the degradation machinery converge to create a transcription elongation checkpoint downstream of promoter-proximal pausing.
Author: Anthony Chun-yin Chiu
Publisher:
ISBN:
Category :
Languages : en
Pages : 221
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Book Description
Transcription is one of the most fundamental processes in cells, governing the conversion of genetic information to RNA. Numerous regulatory mechanisms function to ensure that desired transcripts are being expressed. Promoters transcribe divergently, producing low-abundant upstream antisense RNAs (uaRNAs) in addition to a stable downstream RNAs. Thus, a central question is what mechanisms are sense RNAs more stable compared to most transcription events. It is proposed that an asymmetric distribution of Ul snRNP binding sites and polyadenylation site (PAS) motifs known as the UI-PAS axis regulates early termination of RNA Polymerase II. Here, we generated a conditional knockout of the essential RNA exosome subunit, Exosc3, in mouse embryonic stem cells. Removal of Exosc3 resulted in stabilization of polyadenylated uaRNAs, enhancer RNAs and long noncoding RNAs. In addition, promoter proximal pausing increased modestly upon Exosc3 removal. Interestingly, a large class of polyadenylated short transcripts in the sense direction terminate within the first intron, similar to premature termination observed upon Ul inhibition. Further investigation of these prematurely termination sites revealed they are found at the edges of stable nucleosome free regions demarcated by CpG islands and are suppressed by U1 snRNP. Interestingly, promoter-proximal Pol II pausing consists of two processes: TSS-proximal and +1 stable nucleosome pausing. Genes associated with premature termination have increased +1 stable nucleosome pausing, association of chromatin remodelers and are more sensitive to inhibition by flavopiridol or a Myc inhibitor. Additionally, the nuclear poly(A) binding protein, Pabpnl, promotes degradation of polyadenylated uaRNAs. Most Pabpnl sensitive uaRNAs are also Exosc3 substrates, and sensitivity to Pabpnl inhibition inversely correlates with the proximity of the termination site to the TSS. Interestingly, at uaRNAs and sense RNAs, Pabpnl -sensitive PAS termination events also occur near the first stable nucleosome, similar to Exosc3-sensitive PAS termination events, suggesting that Pabpnl collaborates with Exosc3 to regulate stability of polyadenylated transcripts. Hence, this supports a model whereby Ul snRNP, +1 stable nucleosomes and the degradation machinery converge to create a transcription elongation checkpoint downstream of promoter-proximal pausing.
Author: Torben Heick Jensen
Publisher: Springer Science & Business Media
ISBN: 1441978410
Category : Medical
Languages : en
Pages : 161
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Book Description
The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
Author: Ann Arvin
Publisher: Cambridge University Press
ISBN: 1139461648
Category : Medical
Languages : en
Pages : 1325
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Book Description
This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
Author:
Publisher: Academic Press
ISBN: 9780124047419
Category : Science
Languages : en
Pages : 0
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Book Description
This special volume of The Enzymes is targeted towards researchers in biochemistry, molecular and cell biology, pharmacology, and cancer. This thematic volume discusses Eukaryotic RNases and their partners in RNA degradation and biogenesis.
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1492
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Book Description
Author: Robert Goldberger
Publisher: Springer Science & Business Media
ISBN: 1468434179
Category : Science
Languages : en
Pages : 570
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Book Description
The motivation for us to produce a treatise on regulation was mainly our convic tion that it would be fun, and at the same time productive, to approach the subject in a way that differs from that of other treatises. We had ourselves written reviews for various volumes over the years, most of them bringing together all possible facts relevant to a particular operon, virus, or biosynthetic system. And we were not convinced of the value of such reviews for anyone but the expert in the field reviewed. We thought it might be more interesting and more instructive-for both author and reader-to avoid reviewing topics that anyone scientist might work on, but instead to review the various parts of what many different scientists work on. Cutting across the traditional boundaries that have separated the subjects in past volumes on regulation is not an easy thing to do-not because it is difficult to think of what interesting topics should replace the old ones, but because it is difficult to find authors who possess sufficient breadth of knowledge and who are willing to write about areas outside those pursued in their own laboratories. For example, no one scientist works on suppression per se. He may study the structure of suppressor tRNAs in Escherichia coli, he may study phenotypic suppression of various characters in drosophila, he may study polarity in gene expression, and so on.
Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309452961
Category : Medical
Languages : en
Pages : 583
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Book Description
In the United States, some populations suffer from far greater disparities in health than others. Those disparities are caused not only by fundamental differences in health status across segments of the population, but also because of inequities in factors that impact health status, so-called determinants of health. Only part of an individual's health status depends on his or her behavior and choice; community-wide problems like poverty, unemployment, poor education, inadequate housing, poor public transportation, interpersonal violence, and decaying neighborhoods also contribute to health inequities, as well as the historic and ongoing interplay of structures, policies, and norms that shape lives. When these factors are not optimal in a community, it does not mean they are intractable: such inequities can be mitigated by social policies that can shape health in powerful ways. Communities in Action: Pathways to Health Equity seeks to delineate the causes of and the solutions to health inequities in the United States. This report focuses on what communities can do to promote health equity, what actions are needed by the many and varied stakeholders that are part of communities or support them, as well as the root causes and structural barriers that need to be overcome.
Author: Marcelo E. Tolmasky
Publisher: John Wiley & Sons
ISBN: 1555818986
Category : Science
Languages : en
Pages : 512
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Book Description
Explore the remarkable discoveries in the rapidly expanding field of plasmid biology Plasmids are integral to biological research as models for innumerable mechanisms of living cells, as tools for creating the most diverse therapies, and as crucial helpers for understanding the dissemination of microbial populations. Their role in virulence and antibiotic resistance, together with the generalization of "omics" disciplines, has recently ignited a new wave of interest in plasmids. This comprehensive book contains a series of expertly written chapters focused on plasmid biology, mechanistic details of plasmid function, and the increased utilization of plasmids in biotechnology and pharmacology that has occurred in the past decade. Plasmids: Biology and Impact in Biotechnology and Discovery serves as an invaluable reference for researchers in the wide range of fields and disciplines that utilize plasmids and can also be used as a textbook for upper-level undergraduate and graduate courses in biotechnology and molecular biology.
Author: Nancy L. Craig
Publisher: Oxford University Press, USA
ISBN: 0198788657
Category :
Languages : en
Pages : 1018
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Book Description
A fresh, distinctive approach to the teaching of molecular biology. With its focus on key principles, its emphasis on the commonalities that exist between the three kingdoms of life, and its integrated coverage of experimental methods and approaches, Molecular Biology is the perfect companion to any molecular biology course.
Author: Joseph W. Lengeler
Publisher: John Wiley & Sons
ISBN: 1444313304
Category : Science
Languages : en
Pages : 984
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Book Description
Designed as an upper-level textbook and a reference for researchers, this important book concentrates on central concepts of the bacterial lifestyle. Taking a refreshingly new approach, it present an integrated view of the prokaryotic cell as an organism and as a member of an interacting population. Beginning with a description of cellular structures, the text proceeds through metabolic pathways and metabolic reactions to the genes and regulatory mechanisms. At a higher level of complexity, a discussion of cell differentiation processes is followed by a description of the diversity of prokaryotes and their role in the biosphere. A closing section deals with man and microbes (ie, applied microbiology). The first text to adopt an integrated view of the prokaryotic cell as an organism and as a member of a population. Vividly illustrates the diversity of the prokaryotic world - nearly all the metabolic diversity in living organisms is found in microbes. New developments in applied microbiology highlighted. Extensive linking between related topics allows easy navigation through the book. Essential definitions and conclusions highlighted. Supplementary information in boxes.
