Transcriptional Control Through Elongational Pausing in Drosophila Melanogaster PDF Download
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Author: Eric Brice Rasmussen
Publisher:
ISBN:
Category :
Languages : en
Pages : 364
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Author: Eric Brice Rasmussen
Publisher:
ISBN:
Category :
Languages : en
Pages : 364
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Author: Thomas Paul O'Brien
Publisher:
ISBN:
Category :
Languages : en
Pages : 252
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Author: Gregory T. Booth
Publisher:
ISBN:
Category :
Languages : en
Pages : 404
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Promoter-proximal pausing of RNA Polymerase II (Pol II) is now recognized as a ubiquitous mechanism for regulating gene expression in metazoans. By capturing engaged Pol II shortly after transcription initiation, genes are primed for activation of RNA synthesis, enabling cells to rapidly alter global transcription programs. However, despite conservation of many factors involved in establishing this regulatory platform, many eukaryotes do not control gene expression through this process. Here, the examination of the global transcriptional landscape in two distantly related yeast revealed unprecedented divergence in Pol II distributions across genes. Previously undescribed pause-like profiles were identified within promoter-proximal regions of the fission yeast, Schizosaccharomyces pombe, that are sensitive to loss of the conserved elongation factor, Spt4. Thus, fission yeast might employ a variant of the system of regulation found in higher eukaryotes In flies and mammals, Pol II arrested within the promoter proximal region of a gene can only be released through the activity of a positive-transcription elongation factor (P-TEFb), composed of kinase (Cdk9) and cyclin (CycT1/2) subunits. Investigating the functional impact of Cdk9 on transcription in fission yeast revealed that, unlike most metazoan systems, Pol II in S. pombe is capable of overcoming the early elongation barrier after kinase inhibition, although not without consequence. However, fission yeast lack the metazoan-specific negative elongation factor complex (NELF) involved in pausing, perhaps limiting their ability to control the release of Pol II through phosphorylation of the elongation complex. Ultimately, by depleting pausing factors from cell lines derived from Drosophila melanogaster, it was tested whether NELF is required for P-TEFb-regulated pause escape. While global transcription is largely unaffected by the loss of NELF, upon inhibition of Cdk9, a significant amount of Pol II is aberrantly released from the pause, suggesting reduced control of this regulation. These findings suggest that NELF may have evolutionarily refined an ancestral promoter-proximal architecture of the transcription elongation complex, giving rise to a novel mechanism for gene regulation.
Author: Stephanie Yee
Publisher:
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Category :
Languages : en
Pages :
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"Post-transcriptional control is a critical determinant of gene expression that acts at the level of the messenger RNA (mRNA), which includes processes such as translational control and RNA localization, and is the focus of this thesis. This regulation is in part dictated by the characteristics of the 5’ and 3’ untranslated regions (UTRs) of the mRNA and the cis-elements they harbour. Translational control can occur at the initiation step where the 5’ cap structure of the mRNA is recognized by the eIF4E, whose activity can be modulated by the eIF4E-binding protein (4E-BP), a repressor of translation. The target of rapamycin (TOR) pathway integrates a plethora of signals and impinges on protein synthesis through its action on 4E-BPs and S6 kinases (S6Ks), two well-characterized targets. The TOR/4E-BP/eIF4E axis is known to regulate the translation of subsets of mRNAs with distinct features in their 5’UTRs. In light of recent work that demonstrated dysregulated translation of specific mRNAs in the brains of mice lacking 4E-BP2 and engendering autism spectrum disorder-like phenotypes, we endeavoured to similarly identify mRNAs regulated by d4E-BP in Drosophila. In Chapter 2, we performed ribosome profiling to identify specific mRNAs that are translationally regulated downstream of d4E-BP in the adult fly head, used as a proxy for the brain. Gene ontology (GO) analysis revealed that the corresponding genes of some of the upregulated mRNAs are involved in innate immunity. We determined that upregulated mRNAs possess 5’UTRs that are shorter but more complex. In our effort to validate one of the targets, dS6K, we detected elevated levels of p-RPS6, a readout of dS6K activity, in d4E-BPnull flies. We conclude there are subsets of differentially ribosome-associated mRNAs with distinct 5’UTR features in the d4E-BPnull fly head.Subcellular localization of mRNAs in the Drosophila embryo establishes a molecular asymmetry of maternally-inherited determinants that is essential for its development. Of the hundreds of transcripts that localize to the primordial germ cells at the posterior of the early embryo, only 55 RNAs accumulate around posterior nuclei prior to the development of those cells, termed RNA islands. Many of the genes that encode these mRNAs have established functions in embryonic patterning and germline development. Despite their common destination to RNA islands, a shared localization element has yet to be identified. In Chapter 3, we mapped the localization elements within the 3’UTRs of two transcripts that localize to RNA islands, polar granule component (pgc) and germ cell-less (gcl). Based on deletion mutation analysis, we report that gcl has redundant localization elements, while pgc possesses a localization element in the distal region. We show that the localization of polar granule proteins, Oskar, Tudor and Vasa, and 11 RNAs have conserved posterior localization in Drosophilids. Using recent findings of a sequence motif that contributes to RNA island localization, we found that this motif is enriched in the 3’UTRs of the majority of transcripts that localize in this way. Our data suggests that the RNA island type of posterior localization is an important process for directing the localization of transcripts with key roles in germline development, as highlighted by the many aspects of this process that is conserved"--
Author: Jian Li
Publisher:
ISBN:
Category :
Languages : en
Pages : 159
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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: Ronald C. Conaway
Publisher: Raven Press (ID)
ISBN:
Category : Science
Languages : en
Pages : 600
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Book Description
Presents a coherent account of many productive lines of investigation, organized as a series of mini-reviews that focus on major research areas including studies on the structure and mechanisms of action of bacterial, viral, and eukaryotic RNA polymerases, and the transcription factors that control their activities. Each review provides a brief but up-to-date account of the progress of research in a particular area, a discussion of the major issues and questions driving that research, and a brief description of the evolving approaches and technologies used to address those questions. Annotation copyright by Book News, Inc., Portland, OR
Author: Renato Paro
Publisher: Springer Nature
ISBN: 3030686701
Category : Science
Languages : en
Pages : 215
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Book Description
This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Author: Peter Csermely
Publisher: Springer Science & Business Media
ISBN: 0387399755
Category : Science
Languages : en
Pages : 218
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Book Description
This book makes a novel synthesis of the molecular aspects of the stress response and long term adaptation processes with the system biology approach of biological networks. Authored by an exciting mixture of top experts and young rising stars, it provides a comprehensive summary of the field and identifies future trends.
Author: Akira Nakai
Publisher: Springer
ISBN: 4431558527
Category : Science
Languages : en
Pages : 300
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Book Description
This book presents a large amount of information related to the heat shock response and heat shock factor (HSF), describes core observations about molecular mechanisms and pathophysiological roles, and provides fundamental concepts on the basis of information from diverse aspects. This adaptive response to high temperature or protein misfolding is a fundamental mechanism to maintain the capacity of protein homeostasis, or proteostasis, and is evolutionally conserved among all living organisms, including bacteria and humans, on the earth. Furthermore, physiological and pathological roles of HSF have been extensively studied in fruit fly, worm, and mouse models. It has been revealed that HSF plays roles in development of the brain, reproductive and sensory organs, and in ageing, inflammation, and circadian rhythm. Analysis of the mechanisms have uncovered that HSF exerts a wide range of effects on gene expression and epigenetic status on the whole genome. Moreover, loss or gain of HSF function is also closely related to protein-misfolding diseases including neurodegenerative diseases, psychiatric diseases, heart diseases, and cancers. Therefore, HSF is now thought to be a promising therapeutic target for treatment of these refractory diseases. For undergraduate students, this is a highly understandable source of information on heart shock response and HSF, covering the basis of HSF biology, the physiological role of HSF, and disease associated with HSF function. This book not only serves as a guide to the heat shock response and HSF for students and young researchers in other fields, but also is a cornerstone for future work in the field related to the heat shock response and HSF.
