The Role of Initiation Factor Dynamics in Translation Initiation PDF Download
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Author:
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Languages : en
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Book Description
Like most biological polymerization reactions, ribosome-catalyzed protein synthesis, or translation, can be divided into initiation, elongation, and termination stages. Initiation is the rate-limiting stage of translation and a critical site for translational control of gene expression. Throughout all stages of protein synthesis, the ribosome is aided by essential protein co-factors known as translation factors. I have studied the role that two translation initiation factors, IF1 and IF3, play in the mechanism and regulation of translation initiation in Escherichia coli. Specifically, I have used single-molecule fluorescence resonance energy transfer (smFRET) as a primary tool for investigating how the dynamics of IF1 and IF3 regulate the accuracy with which the translational machinery selects an initiator transfer RNA (tRNA) and the correct messenger RNA (mRNA) start codon during the initiation stage of protein synthesis.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Like most biological polymerization reactions, ribosome-catalyzed protein synthesis, or translation, can be divided into initiation, elongation, and termination stages. Initiation is the rate-limiting stage of translation and a critical site for translational control of gene expression. Throughout all stages of protein synthesis, the ribosome is aided by essential protein co-factors known as translation factors. I have studied the role that two translation initiation factors, IF1 and IF3, play in the mechanism and regulation of translation initiation in Escherichia coli. Specifically, I have used single-molecule fluorescence resonance energy transfer (smFRET) as a primary tool for investigating how the dynamics of IF1 and IF3 regulate the accuracy with which the translational machinery selects an initiator transfer RNA (tRNA) and the correct messenger RNA (mRNA) start codon during the initiation stage of protein synthesis.
Author:
Publisher: Academic Press
ISBN: 9780123739698
Category : Science
Languages : en
Pages : 512
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Book Description
For over fifty years the Methods in Enzymology series has been the critically aclaimed laboratory standard and one of the most respected publications in the field of biochemistry. The highly relevant material makes it an essential publication for researchers in all fields of life and related sciences. This volume, the second of three on the topic of Translation Initiation includes articles written by leaders in the field.
Author: Daniel David MacDougall
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
The data strongly suggest the occurrence of simultaneous occupancy of the ribosome by IF2 and ternary complex, implying that the ribosome is structurally capable of recruiting ternary complex prior to IF2 release from the 70S IC. The observation that the ribosome can accommodate more than one translation factor at a time may have important implications for understanding how it efficiently coordinates factor binding and release throughout protein synthesis, and opens the door to mechanistic studies of the ribosomal L7/L12 stalk, presumed to play a prominent role in these processes.
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:
Publisher: Academic Press
ISBN: 0080889662
Category : Science
Languages : en
Pages : 420
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Book Description
For over fifty years the Methods in Enzymology series has been the critically aclaimed laboratory standard and one of the most respected publications in the field of biochemistry. The highly relevant material makes it an essential publication for researchers in all fields of life and related sciences. This volume, the first of three on the topic of Translation Initiation includes articles written by leaders in the field.
Author: Marina V. Rodnina
Publisher: Springer Science & Business Media
ISBN: 3709102154
Category : Medical
Languages : en
Pages : 428
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Book Description
The ribosome is a macromolecular machine that synthesizes proteins with a high degree of speed and accuracy. Our present understanding of its structure, function and dynamics is the result of six decades of research. This book collects over 40 articles based on the talks presented at the 2010 Ribosome Meeting, held in Orvieto, Italy, covering all facets of the structure and function of the ribosome. New high-resolution crystal structures of functional ribosome complexes and cryo-EM structures of translating ribosomes are presented, while partial reactions of translation are examined in structural and mechanistic detail, featuring translocation as a most dynamic process. Mechanisms of initiation, both in bacterial and eukaryotic systems, translation termination, and novel details of the functions of the respective factors are described. Structure and interactions of the nascent peptide within, and emerging from, the ribosomal peptide exit tunnel are addressed in several articles. Structural and single-molecule studies reveal a picture of the ribosome exhibiting the energy landscape of a processive Brownian machine. The collection provides up-to-date reviews which will serve as a source of essential information for years to come.
Author: Albert Tsai
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Translation is the final step that converts genetic information into proteins composed of amino acids using the ribosome-- a complex molecular machine that coordinates the kinetics, chemistry, and mechanics necessary to synthesize a polypeptide. Translation is highly dynamic with processes taking place on the microseconds to minutes timescales. Among the different techniques employed to probe the dynamics of translation, single-molecule fluorescence occupies a unique position, being able to track heterogeneous compositional and conformational changes occurring within tens of milliseconds to minutes. Leveraging several fluorescent signals, we probed the dynamics of translation initiation. Instead of a linear pathway, we observed several different pathways all leading to the formation of an elongation competent ribosome complex, with the flux through each modulated by initiation factors, tRNAs, and mRNA sequence. Next, we tracked how the aminoglycoside family of antibiotics inhibits ribosome and tRNA dynamics during peptide synthesis (elongation), concluding that their potency as bactericides stems from kinetically inhibiting elongation. Finally, we transitioned from model systems into observing elongation dynamics on a biologically functional protein stall sequence, SecM. Our results suggest that stalling the ribosome requires several precisely-timed peptide-ribosome interactions and that ribosomes stall in a distribution of locations on the SecM sequence. These results demonstrate the power of single-molecule fluorescence to monitor global translation dynamics, as well as highlighting the importance of the temporal dimension in forming a coherent and global mechanism for translation.
Author: Kamiko R. Bressler
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Cap-dependent translation drives the global synthesis of proteins. Under stress conditions global protein production is attenuated, yet the translation of ATF4 is upregulated through uORF- mediated translation initiation. eIF5B has been shown to deliver initiator-tRNA during non-canonical translation initiation. As such, we defined the role of eIF5B in the non-canonical translation of ATF4, and p27. Through polysome profiling and luciferase reporter assays, we confirmed that eIF5B facilitates uORF2-mediated repression of ATF4 translation. We determined that eIF5B has transcriptome-wide effects on signaling pathways, verifying activation of the JNK arm of the MAPK pathway and upregulation of dyskerin. I investigated the role eIF5B has in regulation of p27, and suggest that the mechanism is IRES-dependent. This study furthers the understanding into mechanisms of alternative translation initiation, which is critical to gene expression regulation.
Author: Wan-Jung Christine Lai
Publisher:
ISBN:
Category :
Languages : en
Pages : 223
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Book Description
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.
Author: Greco Hernández
Publisher: Springer
ISBN: 3319394681
Category : Science
Languages : en
Pages : 564
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Book Description
The “omics” era has given a new perspective to the findings on the origin and evolution of the process of translation. This book provides insight into the evolution of the translation process and machinery from a modern perspective. Written by leading experts in molecular biology, this text looks into the origins and evolution of the protein synthetic machinery.
