Identification and Characterization of a Cellular Protein Involved in the Post-transcriptional Regulation of Retroviruses PDF Download
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Author: Hengli Tang
Publisher:
ISBN:
Category :
Languages : en
Pages : 242
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Book Description
Author: Hengli Tang
Publisher:
ISBN:
Category :
Languages : en
Pages : 242
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Book Description
Author: Christopher Bryant Westberg
Publisher:
ISBN:
Category :
Languages : en
Pages : 194
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Author: Nicole M. Placek
Publisher:
ISBN:
Category : Cellular control mechanisms
Languages : en
Pages : 156
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Book Description
Abstract: Both retroviruses and cellular genes rely on post-transcriptional mechanisms to regulate the timing and abundance of their protein product. The post-transcriptional control element (PCE) has been identified in the 5' untranslated regions of mRNAs from selected retroviruses and the cellular gene JunD. PCE containing mRNAs rely on the DExH/D box helicase RNA helicase A (RHA) to specifically facilitate robust synthesis of their protein product. Study of retroviruses has developed approaches to understand both cellular control of gene expression and the dyregulation that contributes to cancer and immunodeficiency. JunD, a member of the activator protein -1 (AP-1) family of transcription factors, is important for transcriptional regulation of growth control genes. Dysregulation of JunD is implicated in cancer and metabolic disease via defects in cell- proliferation and disease-associated apoptosis and can also modulate viral persistence. Studies described here build on the previous characterization of SNV and JunD PCE function in HIV gag-pol reporter plasmids and investigate the parental SNV provirus. The results presented validate the role of PCE in combination with a newly identified a distal element, designated the I,II element, in regulation of balanced expression and translational utilization of SNV mRNA. A key conclusion is that PCE and the distal I,II element comprise a bipartite element that interacts with RNA helicase A to selectively modulate post-transcriptional expression of the unspliced SNV gag mRNA. This thesis also reviews the current and historical literature of JunD gene regulation. Three core areas are described and intriguing essential issues are discussed: i) transcription regulation by AP-1 complexes containing JunD protein, ii) post-translational modification of JunD by Jun-terminal kinase (Jnk) and protein:protein interactions, and iii) regulation of translation intiation by JunD PCE. Lessons learned from the study of retrovirus genes have produced essential knowledge of the JunD transcription factor and contributed to the characterization of a novel axis of transational control of complex RNAs.
Author: Stacey Lynn Hull
Publisher:
ISBN:
Category : RNA viruses
Languages : en
Pages :
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Abstract: The central focus of this dissertation is the identification and characterization of retroviral posttranscriptional control elements that affect protein production from unspliced viral RNA. We identify and characterize a new posttranscriptional control element in the Mason-Pfizer monkey virus 52 long terminal repeat (LTR) that modulates translational efficiency by augmentation of translational initiation. MPMV RU5 is necessary for cytoplasmic expression of HIV-1 gag-pol reporter RNA and also enhances cytoplasmic expression of intronless luc RNA by stimulation of ribosome loading. MPMV RU5 functions independently of any viral proteins and instead directs functional interaction with cellular posttranscriptional modulators to facilitate translational enhancement. This research has illuminated an essential step in viral gene expression and provides a new paradigm for understanding cellular control of the translation process. Secondly, we tested the hypothesis that combination of the MPMV constitutive transport element (CTE) and the MPMV or spleen necrosis virus (SNV) RU5 translational enhancer on a single RNA synergistically augments posttranscriptional gene expression. MPMV CTE functions compatibly with MPMV and SNV RU5 to increase cytoplasmic expression of HIV-1 gag-pol reporter RNA in monkey COS, but not 293 cells. The CTE-interactive cellular proteins, Tap and NXT1, are necessary and sufficient to rescue increased cytoplasmic expression of HIV-1 gag-pol reporter RNA in 293 cells. This work produced the realization that differences in cellular posttranscriptional modulators dramatically affect retroviral protein production. Thirdly, we evaluated the role of SNV RU5 on metabolism of homologous SNV RNA. SNV RU5 increases SNV Gag-GFP fusion protein production from unspliced genomic RNA. The increase in protein is attributable, at least in part, to increased cytoplasmic accumulation of the unspliced SNV transcript. RU5 exerts a distinct effect on the spliced env transcript. Deletion of RU5 has no effect on cytoplasmic accumulation of env RNA, but increases splicing efficiency. Therefore, SNV RU5 modulates metabolism of both unspliced and spliced SNV transcripts and is speculated to contain a RNA splicing suppressor. In summary, this dissertation has identified and characterized a new posttranscriptional control element in MPMV and synergistic interactions among functionally distinct retroviral posttranscriptional control elements and their cellular protein partners. This work also demonstrated an important role for SNV RU5 in SNV genomic RNA.
Author: Nouri Neamati
Publisher: John Wiley & Sons
ISBN: 1118015363
Category : Science
Languages : en
Pages : 710
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Book Description
This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.
Author: Bryan Cullen
Publisher: Oxford University Press
ISBN: 9780199633821
Category : Gene Expression Regulation.
Languages : en
Pages : 220
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Book Description
The first book to specifically cover the molecular biology of retroviruses - of immense importance since the high profile of HIV. International contributors provide detailed reviews of the latest knowledge. An excellent text for both medical and non-medical researchers, it also serves as an illuminating introduction for scientists active in other areas.
Author: Phoebe A. Rice
Publisher: Royal Society of Chemistry
ISBN: 0854042725
Category : Science
Languages : en
Pages : 417
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Book Description
This book provides both in-depth background and up-to-date information in this area. The chapters are organized by general themes and principles, written by experts who illustrate topics with current findings. Topics covered include: - the role of ions and hydration in protein-nucleic acid interactions - transcription factors and combinatorial specificity - indirect readout of DNA sequence - single-stranded nucleic acid binding proteins - nucleic acid junctions and proteins, - RNA protein recognition - recognition of DNA damage. It will be a key reference for both advanced students and established scientists wishing to broaden their horizons.
Author: John F. Atkins
Publisher: Springer Science & Business Media
ISBN: 0387893822
Category : Science
Languages : en
Pages : 473
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Book Description
The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.
Author: Guido Silvestri
Publisher: Springer
ISBN: 303002816X
Category : Medical
Languages : en
Pages : 253
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Book Description
This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Author: Nahum Sonenberg
Publisher: CSHL Press
ISBN: 9780879696184
Category : Gene expression
Languages : en
Pages : 1034
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Book Description
Since the 1996 publication of Translational Control, there has been fresh interest in protein synthesis and recognition of the key role of translation control mechanisms in regulating gene expression. This new monograph updates and expands the scope of the earlier book but it also takes a fresh look at the field. In a new format, the first eight chapters provide broad overviews, while each of the additional twenty-eight has a focus on a research topic of more specific interest. The result is a thoroughly up-to-date account of initiation, elongation, and termination of translation, control mechanisms in development in response to extracellular stimuli, and the effects on the translation machinery of virus infection and disease. This book is essential reading for students entering the field and an invaluable resource for investigators of gene expression and its control.
