Author: Aishwarya Devaraj
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Abstract: Protein synthesis occurs in ribosomes, megadalton RNA-protein machines that use aminoacyl-tRNA (aa-tRNA) molecules to translate messenger RNA (mRNA) with high fidelity. During translation elongation, the ribosome orchestrates 3 major events: decoding, peptidyl transfer and translocation. The process of proteins synthesis is also one of the major targets of antibiotics and hence understanding the basics of ribosome function should provide insight for the development of novel drugs. Genomes are maintained and expressed with remarkable fidelity and the accuracy of each process involved represents a compromise that optimizes the evolutionary fitness of the organism. The process of translation elongation is a complex one, and therefore there are potentially many ways the process can go awry. Chapter 1 introduces translation elongation errors and discusses the differences between missense, nonsense and frameshift errors. Mutations in the ribosome and other translation factors that affect the fidelity of translation elongation are also discussed. Chapter 2 is focused on the ribosomal exit (E) site and its role in maintaining the translational reading frame. It has been proposed that a critical role for the E site is in maintenance of translational reading frame, dependent on codon-anticodon pairing (191). Though several studies support the idea that codon-anticodon interaction in the E site contributes to frame maintenance (167), direct in vivo evidence for this hypothesis has been scant. In chapter 2, we investigated this fundamental question and found that the E site helps to maintain the reading frame, but does not contribute to the accuracy of decoding, as has been suggested (chapter 2, 204). We also showed that the mutation of the 30S E site does not inhibit EF-G-catalyzed translocation, in sharp contrast to the effects of mutations in 50S E site. These data provided evidence that the function of the E site in translocation is largely confined to the 50S subunit. One of the earliest identified examples of translational frameshifting occurs in the prfB gene of E. coli, encoding the peptide release factor 2 (RF2). While the genetic studies have identified the determinants of prfB programmed frameshifting and their relative importance, how these determinants act to promote frameshifting has remained unclear. In chapter 3, we compared ribosomal complexes with various spacer lengths between the SD sequence and P codon. We found that a close juxtaposition of the SD-ASD helix and P codon strongly destabilized P-site tRNA but had little or no effect on RF2-dependent termination or EF-Tu-dependent decoding. These data suggested that the intragenic SD of prfB destabilizes pairing of peptidyl-tRNALeu to the zero-frame CUU and promotes directional movement of the mRNA template with respect to the bound tRNA. In chapter 4, we have isolated 16S rRNA mutations that could suppress a +1 frameshift mutation in E. coli. In one of the screens (where the slippery sequence in the frameshift window had a stop codon), 31 independent mutations were identified and mapped to four different positions, of which C1054U was isolated 28 times. The C1054U mutation has also been isolated previously as a nonsense suppressor. Purine substitutions at this position also increased UGA readthrough and miscoding. While the C1054U mutation significantly increased nonsense readthrough and frameshift errors, the mutation had a hyperaccurate phenotype with respect to decoding (i.e., reduced misreading). Other substitutions at this position also had differential effects on the three reporters (missense, nonsense and frameshift). These interesting observations prompted us to characterize these A-site mutations as well as others in 16S rRNA (C1200U, G1491A and G299A) in vitro to get a better understanding of how the ribosome maintains its high fidelity (chapter 5). We investigated the effect of these mutations on RF2 function and found that all of the mutations tested had a defect in RF2-dependent termination. We directly tested the effect of these mutations on decoding by measuring the rate of GTP hydrolysis in both cognate and near-cognate mRNA. We found that all of the mutations tested (C1200U, G1491A, C1054U, C1054A, and G299A) had a substantial defect in initial selection, increasing the rate of GTP hydrolysis particularly on near-cognate mRNA. We also investigated the effect of these mutations on the stability of various tRNAs in the A site. Of the mutations analyzed, C1054U and G1491A seemed to differentially affect tRNA stability, suggesting that these mutations may stimulate GTP hydrolysis in a different way than the others.
Author:
Publisher: Academic Press
ISBN: 0123864984
Category : Science
Languages : en
Pages : 267
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Book Description
The goal of this volume is to provide a comprehensive mechanistic and quantitative view of the processes that mediate or influence the quality control in translation. In addition to discussing processes with direct contribution to translation fidelity, such as aminoacylation of tRNAs and translation elongation itself, special attention is given to other processes with impact on quality control: detection and elimination of defective mRNAs, recycling and translation re-initiation, mRNA editing, and translational recoding through programmed frame-shifting. - Provides a comprehensive mechanistic and quantitative view of the processes that mediate or influence the quality control in translation - Special attention is given to other processes with impact on quality control: detection and elimination of defective mRNAs, recycling and translation re-initiation, mRNA editing, and translational recoding through programmed frame-shifting
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Book Description
Author: Herbert Weissbach
Publisher: Elsevier
ISBN: 0323141706
Category : Science
Languages : en
Pages : 739
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Book Description
Molecular Mechanisms of Protein Biosynthesis is a collection of papers dealing with cell-free systems at the molecular level, including transfer RNA; the initiation, elongation, and termination processes; ribosome structure and function; mRNA translation; and DNA-directed in vitro protein synthesis. A couple of papers review tRNA, aminoacyl-tRNA synthetases, and aspects of ribosome structure. One paper discusses affinity labeling in the study of binding and catalytic sites of large complex and heterogeneous systems such as the ribosome. The investigator should be aware of the chemically reactive or photoactivatible analogue reacting specifically with one or more ribosomal components. This reaction should be determined if it is dependent on the correct binding of the affinity label at the functional site. Another paper describes the series of reactions in protein synthesis as the process by which the ribosome moves relative to the messenger RNA. Other papers discuss messenger RNA and its translation, DNA-dependent cell-free protein synthesis, as well as the genetics of the translational apparatus. The collection will benefit microbiologists, biotechnologists, and academicians connected with the biological sciences.
Author: B. Kirkwood
Publisher: Springer Science & Business Media
ISBN: 9400940971
Category : Science
Languages : en
Pages : 550
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Book Description
Molecular biology proceeds at unremitting pace to unfold new secrets of the living world. Biology, long regarded as an inexact companion to physics and chemistry, has undergone transformation. Now, chemical and physical principles are tools in understanding highly complex biomolecular processes, whose origin lies in a history of chance, constraint and natural selection. The accuracy of these processes, often remarkably high, is crucial to their self perpetuation, both individually and collectively, as ingredients of the organism as a whole. In this book are presented thirteen chapters which deal with various facets of the accuracy problem. Subjects covered include: the specificity of enzymes; the fidelity of synthesis of proteins; the replication and repair of DNA: general schemes for the enhancement of biological accuracy; selection for an optimal balance between the costs and benefits of accuracy; and the possible relevance of molecular mistakes to the process of ageing. The viewpoints are distinct, yet complementary, and the book as a whole offers to researchers and students the first comprehensive account of this growing field.
Author: Moyra Smith
Publisher: Elsevier
ISBN: 0323915477
Category : Medical
Languages : en
Pages : 396
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Book Description
Progress in Genomic Medicine: From Research to Clinical Application provides a careful synthesis of the foundations, current trends and translational challenges in genomic medicine, clarifying pathways forward and enabling genomic medicine research and implementation across clinical settings and treatment development. Sections address the history and growth of genetic medicine, with a discussion of key studies in syndrome delineations, inherited diseases, biochemical genetics, and chromosome abnormalities, overview clinical applications made possible through genomic advances, with chapters on DNA sequencing for clinical genetic diagnosis, genotype-phenotype correlations in individuals and across populations, new-born screening for treatable genetic disorders, and more. In addition, social, ethical and public health aspects of applying genomic technologies are included throughout. Here, Dr. Smith applies her experience and participation in the field, across its major milestones, to put current research, clinical advances, and ongoing questions in context. Traces the development of the field of genomic medicine, exploring key scientific advances and recent steps forward in clinical translation Considers the influence of genomic medicine on complex and monogenic pathology analysis, treatment plans and therapeutics Ties recent research and clinical advances to their historical context
Author: Vijay Kumar
Publisher: Elsevier
ISBN: 012816364X
Category : Science
Languages : en
Pages : 296
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Book Description
Emerging Concepts in Ribosome Structure, Biogenesis, and Function provides a synthesized overview on all parts in this process. The book begins with an introduction to the ribosome factory, its origin and its evolution of translation. Sections discuss subunits, RNA, protein components, and its emergence as a frontier research area for translational potential in cancer and other diseases. In addition, the book explores current developments in ribosome research, including the emergence of ribosomopathies, how deregulation of ribosome biogenesis can impact disease mechanisms and aging, and the discovery of specialized ribosomes. This book provides the emerging research on ribosomes, their biogenesis, and other important topics on structure and function. Therefore, it will serve as a resourceful introduction for both new researchers and those engaged in interdisciplinary ribosomal research.
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.
Author: Heinz Bielka
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 3112729757
Category : Science
Languages : en
Pages : 340
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Book Description
No detailed description available for "The Eukaryotic Ribosome".
Author: Sabine Müller
Publisher: John Wiley & Sons
ISBN: 3527814531
Category : Science
Languages : en
Pages : 81
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Book Description
Ribozymes Provides comprehensive coverage of a core field in the molecular biosciences, bringing together decades of knowledge from the world’s top professionals in the field Timely and unique in its breadth of content, this all-encompassing and authoritative reference on ribozymes documents the great diversity of nucleic acid-based catalysis. It integrates the knowledge gained over the past 35 years in the field and features contributions from virtually every leading expert on the subject. Ribozymes is organized into six major parts. It starts by describing general principles and strategies of nucleic acid catalysis. It then introduces naturally occurring ribozymes and includes the search for new catalytic motifs or novel genomic locations of known motifs. Next, it covers the development and design of engineered ribozymes, before moving on to DNAzymes as a close relative of ribozymes. The next part examines the use of ribozymes for medicinal and environmental diagnostics, as well as for therapeutic tools. It finishes with a look at the tools and methods in ribozyme research, including the techniques and assays for structural and functional characterization of nucleic acid catalysts. The first reference to tie together all aspects of the multi-faceted field of ribozymes Features more than 30 comprehensive chapters in two volumes Covers the chemical principles of RNA catalysis; naturally occurring ribozymes, engineered ribozymes; DNAzymes; ribozymes as tools in diagnostics and therapy, and tools and methods to study ribozymes Includes first-hand accounts of concepts, techniques, and applications by a team of top international experts from leading academic institutions Dedicates half of its content to methods and practical applications, ranging from bioanalytical tools to medical diagnostics to therapeutics Ribozymes is an unmatched resource for all biochemists, biotechnologists, molecular biologists, and bioengineers interested in the topic.
