Translation Mechanisms
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Translation Mechanisms
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Author : Jacques Lapointe
language : en
Publisher: Springer Science & Business Media
Release Date : 2003-07-31
Translation Mechanisms written by Jacques Lapointe and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003-07-31 with Science categories.
Translation Mechanisms provides investigators and graduate students with overviews of recent developments in the field of protein biosynthesis that are fuelled by the explosive and synergic growth of structural biology, genomics, and bioinformatics. The outstanding progress in our understanding of the structure, dynamics, and evolution of the prokaryotic and eukaryotic translation machinery, as well as applications in medicine and biotechnology, are described in 26 chapters covering recent discoveries on: -the subtleties of tRNA aminoacylation with natural and unnatural amino acids. -the control of mRNA stability, a key step of gene regulation. -ribosome structure and function, in the era of the atomic-crystal resolution of the ribosome. -the regulation of the biosynthesis of the translational machinery components. -the action of a variety of inhibitors of translation and the prospect for clinical studies.
Translation Mechanisms And Control
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Author : Michael B. Mathews
language : en
Publisher:
Release Date : 2018-09-30
Translation Mechanisms And Control written by Michael B. Mathews and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-09-30 with Genetic translation categories.
A subject collection from Cold Spring Harbor Perspectives in Biology.
Translation Mechanisms
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Author : Jacques Lapointe
language : en
Publisher:
Release Date : 2002
Translation Mechanisms written by Jacques Lapointe and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with categories.
Mechanisms Of Translation Initiation Mediated By Mrna Structure
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Author : Wan-Jung Christine Lai
language : en
Publisher:
Release Date : 2019
Mechanisms Of Translation Initiation Mediated By Mrna Structure written by Wan-Jung Christine Lai and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
The initiation of translation is a critical process that controls gene expression in all cells. Dysregulation of translation initiation contributes to the development of pathological conditions, including cancer, diabetes and obesity. Despite the fundamental importance of translation initiation, the essential mechanisms that underlie this process are still unknown. This thesis combines in vitro, in vivo and in silico approaches to test a hypothesis that mRNA secondary structure is a major determinant that governs translational initiation. Using Fr̲ster resonance energy transfer (FRET), we show that mRNAs and long noncoding RNAs (lncRNAs) have an intrinsic propensity to fold in the absence of proteins into structures in which the 5' end and 3' end are ?7 nm apart irrespective of RNA length. In addition, single-molecule FRET measurements demonstrate that, instead of adopting a single structure, each mRNA folds into a dynamic ensemble of structures with multiple end-to-end distances that are within just a few nanometers. Computational estimates suggest that the inherent proximity of the ends is a universal property of most mRNA and lncRNA sequences. Only guanosine-depleted RNA sequences with low sequence complexity are unstructured and exhibit end-to-end distances expected for the random coil conformation of RNA. Based on these observations, we propose a novel model that explains how the universally conserved eukaryotic initiation factor 4G (eIF4G) ? poly(A)-binding protein (PABP) interaction stimulates translation initiation in eukaryotes.We hypothesize that PABP binding to the poly(A) tail can facilitate the recruitment of the cap-binding protein complex, eIF4E?eIF4G, to the 5' end of the mRNA since the 5' and 3' ends of mRNA are intrinsically close. Therefore, the eIF4G ? PABP interaction enhances translation by exploiting the intrinsic closeness of mRNA ends. Our data showed that replacing the natural 3' UTR in model mRNAs with intrinsically unstructured sequences decreases mRNA translation efficiency. We also found that the synergy between the 5' mRNA cap and 3' poly(A) tail in protein synthesis is reduced by the introduction of unstructured sequences into the 3' UTR of mRNA. Gel mobility shift assays show that eIF4E?eIF4G?PABP binding to mRNA is promoted by mRNA secondary structure, suggesting that the synergistic enhancement of translation by the 5' cap and 3' poly(A) tail is mediated through the intrinsic proximity of mRNA ends. In conclusion, our results provide strong evidence that mRNA secondary structure plays a critical role in protein synthesis by facilitating translation initiation through a previously unidentified mechanism. Our studies provide the basis for measuring, computing and manipulating end-to-end distances and secondary structure in mRNAs in research and biotechnology.
Translation In Eukaryotes
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Author : Hans Trachsel
language : en
Publisher: CRC Press
Release Date : 1991-07-24
Translation In Eukaryotes written by Hans Trachsel and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1991-07-24 with Science categories.
This book presents an up-to-date review of the mechanisms and regulation of translation in eukaryotes. Topics covered include the basic biochemical reactions of translation initiation, elongation and termination, and the regulation of these reactions under different physiological conditions and in virus-infected cells. The book belongs on the shelf of everyone interested in translation in eukaryotes, including students and researchers requiring comprehensive overviews of most aspects of translation and instructors who want to cover these topics at an advanced level.
Evaluation Of Mrna Translation Initiation Control Mechanisms Under Cellular Stress Conditions
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Author : Ryan Alexander Coots
language : en
Publisher:
Release Date : 2016
Evaluation Of Mrna Translation Initiation Control Mechanisms Under Cellular Stress Conditions written by Ryan Alexander Coots and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Control of mRNA translation is a critical aspect of cell physiology. Translation is primarily controlled at the level of initiation, which has been studied primarily in the context of two regulatory proteins. The 4EBP-1 protein inhibits 5' cap-binding proteins known to assist in ribosome recruitment, while the eIF2[alpha] protein serves an important role in regulating availability of the ternary complex. mTORC1, the kinase of 4EBP-1, is well-known as a translational regulator. However hypophosphorylation of 4EBP-1 has only marginal effects on translation rates. GCN2, the amino acid sensing kinase of eIF2[alpha], was long thought to only sense uncharged tRNAs. However recent work has implicated GCN2 in a variety of metabolic pathways. The extent of GCN2's regulatory control had not been thoroughly evaluated within the context of translation. While both 4EBP1 and eIF2[alpha] are controlled by phosphorylation, the extent of their translational repression differs. Increased phosphorylation of eIF2[alpha] alone seems to have dramatic effects on mRNA translation during starvation, but a phosphorylation reduction on 4EBP-1 does not have as drastic an effect. To understand why eIF2[alpha] had a greater effect on translation than 4EBP-1, I used non-phosphorylatable eIF2[alpha] MEFs to probe translation inititiation. I observed i that these mutant cells have sustained translation despite decreased phosphorylation of 4EBP-1. I show that this sustained translation is cap-independent, fulfilled by m6A modifications on mRNA, and is carried out by interacting METTL3 and ABCF1 proteins. This work helps to explain why the 4EBP-1 protein has marginal effects in regulating translation initiation, and sheds light on why TOP mRNAs have a special sensitivity to mTORC1 status. To more fully understand what roles GCN2 has in translation, I conducted phosphoproteomics with GCN2 WT and KO MEFs to isolate GCN2-dependent phosphoproteins. I show that many proteins rely on GCN2 for phosphorylation changes, and several translation-related phosphoproteins undergo phosphorylation changes in response to amino acid starvation. This experiment provides researchers with a useful dataset to evaluate GCN2-dependent phosphoproteins and demonstrates that GCN2 has broader cellular effects than have been previously identified. Collectively, this thesis pushes forward our understanding of mRNA translation initiation. ii.
Translation And Its Regulation In Cancer Biology And Medicine
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Author : Armen Parsyan
language : en
Publisher: Springer
Release Date : 2014-10-13
Translation And Its Regulation In Cancer Biology And Medicine written by Armen Parsyan and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-10-13 with Medical categories.
This book, for the first time, comprehensively assembles and analyzes a large body of information on the role of the fundamental mechanism of the protein biosynthesis pathway, translation, in cancer biology. It systematically explores the function of the translation machinery and its regulation, including cell signaling, in the development, maintenance and progression of human cancer. The work presented here unveils the tremendous potential and applications of this vast and exciting branch of genetic, biochemical and molecular science in cancer medicine and drug development. Chapters contributed by experts in the field take the reader on a journey that starts with a dissection of the translation machinery and its regulation in norm and cancer. Later chapters characterize etiological and pathogenetic roles that translation plays in specific cancer types. Various aspects of diagnostic, prognostic and therapeutic significance of the translation machinery and its control in cancer are discussed. Readers will discover the importance of the process of translation and its regulatory mechanisms in physiology and cancer biology. The chapters and the numerous illustrations included here were contributed by expert scientists and clinicians from renowned academic and clinical establishments in Canada, the United States of America, the United Kingdom, Italy, France, Belgium, Spain, Germany and Australia. The book conveys information and knowledge that may interest a broad range of students and scholars ranging from basic scientists to clinicians and drug developers seeking to better understand the protein synthesis and its aberrations in cancer biology and cancer medicine.
Structural Insights Into Noncanonical Mechanisms Of Translation
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Author : Nathan Rhys James
language : en
Publisher:
Release Date : 2017
Structural Insights Into Noncanonical Mechanisms Of Translation written by Nathan Rhys James and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
Dissecting Fundamental Mechanisms Of Protein Translation In Saccharomyces Cerevisiae
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Author : Dustin Howard Hite
language : en
Publisher:
Release Date : 2013
Dissecting Fundamental Mechanisms Of Protein Translation In Saccharomyces Cerevisiae written by Dustin Howard Hite and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
The central dogma of biology states that DNA, the genetic information, is transcribed into RNA, an information containing intermediate, which is then translated into proteins, actionable molecules which perform the majority of tasks required for life. To synthesize proteins, the cell employs a massive, macromolecular machine, the ribosome, and a myriad of protein factors to successfully translate an mRNA. My graduate studies have focused both on the ribosome and the protein translation factors that interact with the ribosome to facilitate translation initiation, elongation, and termination. First, utilizing recent advances in high throughput sequencing, we discovered that sequencing of ribosome protected fragments could illuminate in vivo dynamics of ribosome structural changes in Saccharomyces cerevisiae. We demonstrated that the ribosome protects two distinct sizes of fragments and assigned each fragment population to approximate stages of the translation elongation cycle where large structural rearrangements of the ribosome are known to occur. Once these assignments were made, we were able to model elongation speed and demonstrated that, contrary to previous reports, tRNA abundance and codon optimality were not the major determinants of elongation speed; surprisingly our data indicated that the polarity of the amino acid being decoded dictated elongation rates under these conditions, with polar amino acids acting to slow elongation rates. This study also implicated Dom34, a known NO GO decay factor, as a novel component of canonical translation termination and ribosome recycling. Second, we used another genome-wide assay of translation, "gradient encoding" microarray analysis, to interrogate the genome-wide effects of depleting five individual translation factors. Based on the current understanding of the molecular mechanisms of each translation factor, we hypothesized that the depletion of each factor would result in differential translation of mRNAs based on the physical properties of each mRNA species. However, we were startled to observe that the translational program of S. cerevisiae was relatively unperturbed by the depletion of three initiation factors, one elongation factor, and one termination factor. Further investigation revealed that yeast were actively compensating for the deficiency of each factor by either increasing or decreasing translation initiation rates such that the depleted factor was no longer limiting. This tuning was mediated by changes in eIF2[alpha] phosphorylation levels, a known modulator of translation initiation. Overall, we have leveraged high throughput technologies to provide novel understanding of in vivo structural dynamics of the ribosome and reveal a novel, unexpected robustness of the translational program in S. cerevisiae.
Mechanisms Ii Translation Transcription And Structural Properties
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Author :
language : en
Publisher:
Release Date : 1976
Mechanisms Ii Translation Transcription And Structural Properties written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1976 with categories.