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Author: Alexander Orest Subtelny Publisher: ISBN: Category : Languages : en Pages : 144
Book Description
Poly(A) tails are found at the 3' ends of nearly all eukaryotic messenger RNAs (mRNAs) and long non-coding RNAs. The presence of a poly(A) tail promotes translation and inhibits decay of an mRNA, with both effects mediated through poly(A)-binding protein. However, an understanding of the relationship between the length of a poly(A) tail and these aspects of mRNA metabolism has been limited, primarily because of the lack of a technology that provides high-resolution poly(A)-tail length measurements in a global manner. This dissertation describes a new, high-throughput-sequencing-based method (PAL-seq) that measures the tails of individual mRNA molecules by coupling a fluorescence-based readout of poly(A)-tail length with sequencing of the poly(A)-proximal region. Using PAL-seq, we have found that poly(A)-tail lengths exhibit a notably poor correlation with translational efficiency (as measured by ribosome profiling) across genes in nearly all systems we have examined. In contrast, early zebrafish and Xenopus laevis embryos display a striking correlation (Spearman R > 0.6) that disappears at gastrulation. This developmental uncoupling of tail length and translational efficiency explains the different outcomes of microRNA (miRNA)-mediated poly(A)-tail shortening in zebrafish embryos before and after gastrulation, with translational repression being the predominant effect before and mRNA destabilization after. We have also observed that poly(A)-tail lengths do not correlate positively with mRNA half-lives in mammalian cells, and that miRNAs do not promote any apparent tail shortening in this setting. Since these results could be explained by differences in deadenylation rates, we performed a kinetic analysis in which we captured newly-made mRNAs of different age ranges. The deadenylation rates that we calculated after measuring tails over time correlated strongly with mRNA half-lives (Spearman R
Author: Alexander Orest Subtelny Publisher: ISBN: Category : Languages : en Pages : 144
Book Description
Poly(A) tails are found at the 3' ends of nearly all eukaryotic messenger RNAs (mRNAs) and long non-coding RNAs. The presence of a poly(A) tail promotes translation and inhibits decay of an mRNA, with both effects mediated through poly(A)-binding protein. However, an understanding of the relationship between the length of a poly(A) tail and these aspects of mRNA metabolism has been limited, primarily because of the lack of a technology that provides high-resolution poly(A)-tail length measurements in a global manner. This dissertation describes a new, high-throughput-sequencing-based method (PAL-seq) that measures the tails of individual mRNA molecules by coupling a fluorescence-based readout of poly(A)-tail length with sequencing of the poly(A)-proximal region. Using PAL-seq, we have found that poly(A)-tail lengths exhibit a notably poor correlation with translational efficiency (as measured by ribosome profiling) across genes in nearly all systems we have examined. In contrast, early zebrafish and Xenopus laevis embryos display a striking correlation (Spearman R > 0.6) that disappears at gastrulation. This developmental uncoupling of tail length and translational efficiency explains the different outcomes of microRNA (miRNA)-mediated poly(A)-tail shortening in zebrafish embryos before and after gastrulation, with translational repression being the predominant effect before and mRNA destabilization after. We have also observed that poly(A)-tail lengths do not correlate positively with mRNA half-lives in mammalian cells, and that miRNAs do not promote any apparent tail shortening in this setting. Since these results could be explained by differences in deadenylation rates, we performed a kinetic analysis in which we captured newly-made mRNAs of different age ranges. The deadenylation rates that we calculated after measuring tails over time correlated strongly with mRNA half-lives (Spearman R
Author: Rebecca Fry Publisher: Academic Press ISBN: 0128015683 Category : Medical Languages : en Pages : 285
Book Description
Systems Biology in Toxicology and Environmental Health uses a systems biological perspective to detail the most recent findings that link environmental exposures to human disease, providing an overview of molecular pathways that are essential for cellular survival after exposure to environmental toxicants, recent findings on gene-environment interactions influencing environmental agent-induced diseases, and the development of computational methods to predict susceptibility to environmental agents. Introductory chapters on molecular and cellular biology, toxicology and computational biology are included as well as an assessment of systems-based tools used to evaluate environmental health risks. Further topics include research on environmental toxicants relevant to human health and disease, various high-throughput technologies and computational methods, along with descriptions of the biological pathways associated with disease and the developmental origins of disease as they relate to environmental contaminants. Systems Biology in Toxicology and Environmental Health is an essential reference for undergraduate students, graduate students, and researchers looking for an introduction in the use of systems biology approaches to assess environmental exposures and their impacts on human health. Provides the first reference of its kind, demonstrating the application of systems biology in environmental health and toxicology Includes introductions to the diverse fields of molecular and cellular biology, toxicology, and computational biology Presents a foundation that helps users understand the connections between the environment and health effects, and the biological mechanisms that link them
Author: Stephen William Eichhorn Publisher: ISBN: Category : Languages : en Pages : 286
Book Description
Eukaryotic mRNAs have a cap structure at their 5' ends and a poly(A) tail at their 3' ends, and the proteins that bind these features increase the stability and translation of an mRNA. The influence of the poly(A) tail on translation was discovered decades ago, but primarily with regard to the idea that an mRNA with a poly(A) tail is better translated than one without. The influence of differences in tail length on translation had been assessed for just a few mRNAs, and in these cases long-tailed mRNAs were better translated than short-tailed mRNAs. We measured the poly(A)-tail length and translational efficiency of mRNAs corresponding to thousands of different genes in 35 different cell types or contexts. Extending previous singlegene studies, we found a global relationship between tail length and translational efficiency in Drosophila oocytes, and Drosophila, Xenopus, and zebrafish embryos. Surprisingly, in all three species, the strong coupling between tail length and translational efficiency was lost once the embryos reached gastrulation, and there was no coupling in the post-embryonic contexts we examined. We thus demonstrated that poly(A)-tail length is a major determinant of translational efficiency during early animal development and discovered a broadly conserved developmental switch in translational control. During the tail-length regulatory regime of the early embryo, a protein or microRNA might regulate translation by changing the poly(A)-tail length of an mRNA, interacting with the translation machinery, or both mechanisms. We characterized the mechanism used by two translational regulatory proteins in Drosophila, finding that they predominantly act by regulating tail length. Likewise, in early zebrafish embryos, microRNAs repress the translation of their hundreds of mRNA targets by shortening poly(A) tails. Our findings indicate that much of the translational regulation in early development is achieved by regulating poly(A)-tail lengths. Outside of early embryonic contexts, microRNAs regulate gene expression by causing both translational repression and mRNA degradation. We greatly expanded the mammalian cell types and contexts in which the steady-state and pre-steady-state effects of a microRNA had been examined globally for endogenous mRNAs. In all post-embryonic contexts with substantial microRNA-mediated repression, the predominant mode of repression was mRNA degradation.
Author: Nahum Sonenberg Publisher: CSHL Press ISBN: 9780879696184 Category : Gene expression Languages : en Pages : 1034
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: Paolo Sassone-Corsi Publisher: Springer ISBN: 3319270699 Category : Medical Languages : en Pages : 141
Book Description
Recent years have seen spectacular advances in the field of circadian biology. These have attracted the interest of researchers in many fields, including endocrinology, neurosciences, cancer, and behavior. By integrating a circadian view within the fields of endocrinology and metabolism, researchers will be able to reveal many, yet-unsuspected aspects of how organisms cope with changes in the environment and subsequent control of homeostasis. This field is opening new avenues in our understanding of metabolism and endocrinology. A panel of the most distinguished investigators in the field gathered together to discuss the present state and the future of the field. The editors trust that this volume will be of use to those colleagues who will be picking up the challenge to unravel how the circadian clock can be targeted for the future development of specific pharmacological strategies toward a number of pathologies.
Author: Jacques Lapointe Publisher: Springer Science & Business Media ISBN: 9780306478390 Category : Science Languages : en Pages : 476
Book Description
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.
Author: Publisher: Academic Press ISBN: 0128171944 Category : Medical Languages : en Pages : 444
Book Description
RNA-based Regulation in Human Health and Disease offers an in-depth exploration of RNA mediated genome regulation at different hierarchies. Beginning with multitude of canonical and non-canonical RNA populations, especially noncoding RNA in human physiology and evolution, further sections examine the various classes of RNAs (from small to large noncoding and extracellular RNAs), functional categories of RNA regulation (RNA-binding proteins, alternative splicing, RNA editing, antisense transcripts and RNA G-quadruplexes), dynamic aspects of RNA regulation modulating physiological homeostasis (aging), role of RNA beyond humans, tools and technologies for RNA research (wet lab and computational) and future prospects for RNA-based diagnostics and therapeutics. One of the core strengths of the book includes spectrum of disease-specific chapters from experts in the field highlighting RNA-based regulation in metabolic & neurodegenerative disorders, cancer, inflammatory disease, viral and bacterial infections. We hope the book helps researchers, students and clinicians appreciate the role of RNA-based regulation in genome regulation, aiding the development of useful biomarkers for prognosis, diagnosis, and novel RNA-based therapeutics. Comprehensive information of non-canonical RNA-based genome regulation modulating human health and disease Defines RNA classes with special emphasis on unexplored world of noncoding RNA at different hierarchies Disease specific role of RNA - causal, prognostic, diagnostic and therapeutic Features contributions from leading experts in the field
Author: Lucy W. Barrett Publisher: Springer Science & Business Media ISBN: 3034806795 Category : Science Languages : en Pages : 63
Book Description
There is now compelling evidence that the complexity of higher organisms correlates with the relative amount of non-coding RNA rather than the number of protein-coding genes. Previously dismissed as “junk DNA”, it is the non-coding regions of the genome that are responsible for regulation, facilitating complex temporal and spatial gene expression through the combinatorial effect of numerous mechanisms and interactions working together to fine-tune gene expression. The major regions involved in regulation of a particular gene are the 5’ and 3’ untranslated regions and introns. In addition, pervasive transcription of complex genomes produces a variety of non-coding transcripts that interact with these regions and contribute to regulation. This book discusses recent insights into the regulatory roles of the untranslated gene regions and non-coding RNAs in the control of complex gene expression, as well as the implications of this in terms of organism complexity and evolution.
Author: Joanna Rorbach Publisher: Humana ISBN: 9781493960552 Category : Medical Languages : en Pages : 0
Book Description
In Polyadenylation: Methods and Protocols, expert researchers in the field detail many of the protocols which are now commonly used to study polyadenylation. Focusing on recent advances in the fast-moving polyadenylation filed, that has recently been recognized as a key contributor to the complexity of mammalian gene expression. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and key tips on troubleshooting and avoiding known pitfalls.
Author: Alexander Orest Subtelny
Author: Alexander Orest Subtelny
Author: Rebecca Fry
Author: Stephen William Eichhorn
Author: Nahum Sonenberg
Author: Bruce Alberts
Author: Paolo Sassone-Corsi
Author: Jacques Lapointe
Author: 
Author: Lucy W. Barrett
Author: Joanna Rorbach