Download or read book Alterations in Translational Control by EIF4E Homologous Protein 4EHP written by Valerie Henderson and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Translational Control by Eukaryotic Initiation Factor eIF 4E and 4G Homologous Proteins written by Ramona Weber and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: All living systems rely on appropriate protein synthesis and therefore evolved intricate mechanisms to control their proteome. Especially, the complexity of metazoan multicellular processes requires a strict and multilayered regulation of gene expression at the level of transcription, mRNA processing, translation, mRNA stability, and protein modifications and stability. Here, I present work on two research projects that uncovered the hitherto unidentified roles of translation initiation (1) and mRNA decay factors (2) specialized in controlling unconventional mRNA translation and co-translational mRNA stability, respectively. The initiation step of translation commences with the assembly of the eukaryotic initiation factor 4F (eIF4F) complex on the mRNA 5 ́ cap structure which facilitates the recruitment of the ribosome to mediate protein synthesis. The eIF4F consists of the cap-binding protein eIF4E, the RNA helicase eIF4A and the scaffolding factor eIF4G. Apart from eIF4G, metazoan cells express other eIF4G-like proteins: eIF4G2 - a.k.a. DAP5/p97/NAT1 - and eIF4G3. Although the different homologs perform non-redundant functions in translation, we lack detailed understanding of their individual contribution to the initiation of protein synthesis. To gain insights into the function of DAP5 in translation initiation, I applied transcriptome (RNA- sequencing) and translatome (ribosome profiling) approaches to CRISPR-Cas9 engineered human HEK293T DAP5-null cells. These approaches allowed the identification of a group of mRNAs with complex 5 ́ untranslated regions (UTRs) that required the DAP5-eIF4A complex for efficient translation. In detail, the 5 ́ UTRs of DAP5 targets harbor strong secondary structures and at least one upstream open reading frame (uORF) that normally sequesters ribosomes from initiation at the main ORF (mORF). In this context, DAP5 is critical for mORF translation as it mediates re-initiation after uORF translation. Taken together, my studies on DAP5 demonstrate how cells control translation initiation using 5 ́ UTR-associated mechanisms. Regulation of translation initiation can also involve additional cap-binding proteins. The eIF4E-homologous protein (4EHP) competes with eIF4E to bind the mRNA 5 ́ cap structure. Unlike eIF4E, 4EHP does not promote translation since it is unable to recruit eIF4G and the ribosome. Instead, 4EHP represses translation and induces mRNA decay with the help of 4EHP-binding factors. The GIGYF1 and GIGYF2 proteins specifically associate with 4EHP and act as scaffolding proteins for GYF domain-associated proteins like tristetraprolin (TTP) or ZNF598, the RNA helicase and decapping activator DDX6, and NOT1 - a subunit of the CCR4-NOT deadenylase complex. When recruited to an mRNA, the 4EHP-GIGYF1/2 6 complexes thus elicit translation repression and mRNA decay. Although the molecular mechanisms have been studied in great detail, we only have sparse information on the pool of mRNAs subjected to 4EHP-GIGYF1/2 mediated repression and decay. Analysis of RNA- sequencing and ribosome profiling datasets of 4EHP- and GIGYF1/2-null cells revealed that the 4EHP-GIGYF1/2 complexes co-translationally target mRNAs with perturbed ribosome elongation or specific nascent peptide chains for decay. These include, among others, mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, a- and b-tubulin subunits and mRNAs with CAG codon repeats encoding poly-glutamine (Q) stretches. In detail, the 4EHP- GIGYF1/2 complexes are recruited to target mRNAs via the GYF domain-associated proteins and upon binding to the mRNA 5 ́ cap, and DDX6, degrade the bound mRNA. My studies show for the first time how a repressive complex, associated with neurological disorders in animal models and affected humans, specifically minimizes the protein output of a subset of mRNAs. Altogether, I identified a previously unappreciated role of the 4EHP-GIGYF1/2 complexes in maintaining protein homeostasis and preventing excessive production of potentially toxic proteins. In summary, my studies increase our understanding of how metazoan cells utilize the translation control toolbox to fine-tune their proteome and react to developmental cues, adapt to environmental changes and maintain homeostasis. The identified translational programs are fundamental for establishing a multicellular organization but at the same time allow the organism to evade cancer and neurological diseases.
Download or read book The Oxford Handbook of Neuronal Protein Synthesis written by Wayne S. Sossin and published by Oxford University Press. This book was released on 2021 with total page 676 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook is currently in development, with individual articles publishing online in advance of print publication. At this time, we cannot add information about unpublished articles in this handbook, however the table of contents will continue to grow as additional articles pass through the review process and are added to the site. Please note that the online publication date for this handbook is the date that the first article in the title was published online.
Download or read book Identification and Characterisations of a Novel Posttranslational Modification of Translation Repressor 4E BP2 written by Michael Anthony Bidinosti and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Oxford Handbook of Neuronal Protein Synthesis written by Wayne S. Sossin and published by Oxford University Press. This book was released on 2021-04-15 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Translational control in the nervous system is important. Many physiological processes in the nervous system depend on accurate control of the proteome that is mediated through protein synthetic mechanisms and thus, the nervous system is very sensitive to dysregulation of translational control. The Oxford Handbook of Neuronal Protein Synthesis reviews the mechanisms of translational control used by the nervous system, as well as how important nervous system functions, such as plasticity and homeostasis, depend on accurate translational control. The handbook extensively covers how dysregulation of protein synthesis can manifest itself in many distinct pathological processes including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. The handbook is comprehensive in its coverage of translational control mechanisms with particular focus on how these general control mechanisms are specifically utilized in the context of the cell biological constraints of the nervous system from both a mechanistic and systems perspective.
Download or read book International Review of Cytology written by Kwang W. Jeon and published by Elsevier. This book was released on 2006-02-20 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: International Review of Cytology presents current advances and comprehensive reviews in cell biology – both plant and animal. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research. Articles in this volume address new insights into fatty acid modulation of pancreatic beta cell function; drosophila RNA binding proteins; plasticity of pelvic autonomic ganglia and urogenital innervation; vomeronasal vs. olifactory epithelium: cellular basis for human vomeronasal perception; and tight junctions.
Download or read book Translation and Its Regulation in Cancer Biology and Medicine written by Armen Parsyan and published by Springer. This book was released on 2014-10-13 with total page 709 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book MicroRNAs written by Krishnarao Appasani and published by Cambridge University Press. This book was released on 2009-08-20 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their recent discovery is revolutionising both basic biomedical research and drug discovery. Expression levels of MiRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand this emerging technology. From the discovery of miRNAs and their functions to their detection and role in disease biology, this volume uniquely integrates the basic science with industry application towards drug validation, diagnostic and therapeutic development. Forewords by: Sidney Altman, Yale University, Winner of the Nobel Prize in Chemistry, 1989 and Victor R. Ambros, Dartmouth Medical School, Co-discoverer of MicroRNAs
Download or read book Translational Control of Gene Expression written by Nahum Sonenberg and published by CSHL Press. This book was released on 2001 with total page 1034 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Chemical Abstracts written by and published by . This book was released on 2002 with total page 2540 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Translation Mechanisms written by Jacques Lapointe and published by Springer Science & Business Media. This book was released on 2003-07-31 with total page 476 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Epigenetics and Reproductive Health written by and published by Academic Press. This book was released on 2020-10-02 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics and Reproductive Health, a new volume in the Translational Epigenetics series, provides a thorough overview and discussion of epigenetics in reproduction and implications for reproductive medicine. Twenty international researchers discuss epigenetic mechanisms operating during the formation of male and female gametes, fertilization and subsequent embryo and placental development, particularly in mammals and transgenerational epigenetic inheritance. This volume also addresses aberrant epigenetic changes influencing male and female infertility, pregnancy related disorders, and those potentially linked to therapeutic manipulations and assisted reproductive technologies. Emphasis is placed on identifying biomarkers for early detection of aberrant epigenetic mechanisms. Later chapters examine the possibility of correcting these epigenetic dysfunctions, as well as current challenges and next steps in research, enabling new translational discoveries and efforts towards developing therapeutics. Thoroughly examines the influence of aberrant epigenetics during gametogenesis and embryogenesis, affecting parents, gametes and embryos, offspring and future generations Explores health outcomes for reproductive senescence, endocrine disruption, testicular cancer, prostrate cancer, breast cancer, ovarian, cancer, endometrial cancer and cervical cancers Features chapter contributions from international researchers in the field
Download or read book The Eukaryotic Ribosome written by Heinz Bielka and published by Walter de Gruyter GmbH & Co KG. This book was released on 1982-12-31 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: No detailed description available for "The Eukaryotic Ribosome".
Download or read book Post transcriptional Mechanisms in Endocrine Regulation written by K.M.J. Menon, PhD and published by Springer. This book was released on 2015-12-30 with total page 347 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book examines how post-transcriptional mechanisms control endocrine function. This includes newly identified regulatory mechanisms involved in hormone biosynthesis, control of hormone receptors and the outputs of hormone mediated signal transduction. Chapters address endocrine hormones including protein peptide/peptide, steroid, and non-steroidal hormones. The impacts of these mechanisms on disease and health are covered, providing a novel update to the scientific literature. Post-transcriptional regulatory mechanisms play an essential role in controlling dynamic gene expression. The outcome of this regulation includes control of the amount, timing, and location of protein expression. Regulation is mediated by cis-acting RNA sequences and structures and transacting RNA binding proteins and non-coding RNAs, including microRNAs. Recent advances in characterization of these regulatory factors have revealed enormous regulatory potential.
Download or read book RNA protein Interactions written by Kiyoshi Nagai and published by Oxford University Press, USA. This book was released on 1994 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of RNA-protein interactions is crucial to understanding the mechanisms and control of gene expression and protein synthesis. The realization that RNAs are often far more biologically active than was previously appreciated has stimulated a great deal of new research in this field. Uniquely, in this book, the world's leading researchers have collaborated to produce a comprehensive and current review of RNA-protein interactions for all scientists working in this area. Timely, comprehensive, and authoritative, this new Frontiers title will be invaluable for all researchers in molecular biology, biochemistry and structural biology.
Download or read book Evolution of the Protein Synthesis Machinery and Its Regulation written by Greco Hernández and published by Springer. This book was released on 2016-08-10 with total page 564 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Translational Control written by John W. B. Hershey and published by . This book was released on 1996 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive account of recent research in translational control and the molecular mechanisms involved, focusing on the numerous control mechanisms observed in eukaryotes. Subjects include basic mechanisms; the role of phosphorylation; regulation by trans-acting proteins; effects of viral infection; and mRNA stability. Other topics include translational control mediated by upstream AUG codons; a comparative view of initiation site selection mechanisms; and genetics of mitochondrial translation. For researchers with interests in gene expression, RNA biology, and protein synthesis. Annotation copyright by Book News, Inc., Portland, OR
