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Author: Katherine Lee Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
The oocyte-to-embryo transition (OET) occurs in the absence of new transcription and relies on post-transcriptional gene regulation, including translational control by mRNA poly(A) tail regulation, where cytoplasmic polyadenylation activates translation and deadenylation leads to translational repression and decay. However, how the transcriptome-wide landscape of mRNA poly(A) tails shapes translation across the OET in mammals remains unknown. Here, we performed long-read RNA sequencing to uncover poly(A) tail lengths and mRNA abundance transcriptome-wide in mice across five stages of development from oocyte to embryo. Integrating these data with recently published ribosome profiling data, we demonstrate that poly(A) tail length is coupled to translational efficiency across the entire OET. We uncover an extended wave of global deadenylation during fertilization, which sets up a switch in translation control between the oocyte and embryo. In the oocyte, short-tailed maternal mRNAs that resist deadenylation in the oocyte are translationally activated, whereas large groups of mRNAs deadenylated without decay in the oocyte are later readenylated to drive translation activation in the early embryo. To investigate the mechanism, we have identified 3'UTR sequence motifs in activated and repressed transcripts and identified stage-specific candidates for RNA binding protein regulators. Our findings provide an important resource and insight into the mechanisms by which cytoplasmic polyadenylation and deadenylation dynamically shape poly(A) tail length in a stage-specific manner to orchestrate development from oocyte to embryo in mammals.
Author: Katherine Lee Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
The oocyte-to-embryo transition (OET) occurs in the absence of new transcription and relies on post-transcriptional gene regulation, including translational control by mRNA poly(A) tail regulation, where cytoplasmic polyadenylation activates translation and deadenylation leads to translational repression and decay. However, how the transcriptome-wide landscape of mRNA poly(A) tails shapes translation across the OET in mammals remains unknown. Here, we performed long-read RNA sequencing to uncover poly(A) tail lengths and mRNA abundance transcriptome-wide in mice across five stages of development from oocyte to embryo. Integrating these data with recently published ribosome profiling data, we demonstrate that poly(A) tail length is coupled to translational efficiency across the entire OET. We uncover an extended wave of global deadenylation during fertilization, which sets up a switch in translation control between the oocyte and embryo. In the oocyte, short-tailed maternal mRNAs that resist deadenylation in the oocyte are translationally activated, whereas large groups of mRNAs deadenylated without decay in the oocyte are later readenylated to drive translation activation in the early embryo. To investigate the mechanism, we have identified 3'UTR sequence motifs in activated and repressed transcripts and identified stage-specific candidates for RNA binding protein regulators. Our findings provide an important resource and insight into the mechanisms by which cytoplasmic polyadenylation and deadenylation dynamically shape poly(A) tail length in a stage-specific manner to orchestrate development from oocyte to embryo in mammals.
Author: Omar Karl Vieux Publisher: ISBN: Category : Languages : en Pages :
Book Description
"Precise regulation of gene expression is indispensable for proper cell function. This challenge is particularly complex in oocytes where transcription is active during growth but is undetectable in fully grown oocytes and during meiotic maturation. Transcripts required to drive oocyte maturation and early post-fertilization embryogenesis are therefore synthesized in growing oocytes and kept translationally silent until the appropriate time. RNA processing mechanisms play central roles in regulating translation and are indispensable for timely and successful oogenesis. In Manuscript I, an RNA processing mechanism is described in the oocyte. Maternal transcripts are categorized according to their poly(A) tail length at different stages of oocyte development. Type I and Type II transcripts are deadenylated and polyadenylated, respectively, during maturation. Type III transcripts are polyadenylated in the first half of maturation and deadenylated in the second half of maturation. CNOT6, a key component of the CCR4-NOT deadenylase complex, requires Pumilio and FBF binding elements (PBE) to deadenylate type III transcripts. Surprisingly however, the modulation of the poly(A) tail does not affect RNA translation and turnover in the oocyte. In Manuscript II, a novel type of RNP is described in cold-shocked oocytes. Inducible 18033 granules are identified as a novel type of stress granules whose formation is controlled by oocyte cell cycle regulators. More specifically, CDK1 activity prevents the formation of the granules at the later stages of maturation. A functional reporter gene assay also reveals a protective role for 18033 granules, preventing the non-reversible inhibition of translation in cold-shocked oocytes. The results described in this thesis highlight different facets of RNA metabolism in the oocyte and explore their role during maturation in producing eggs." --
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: Florence Louise Marlow Publisher: Morgan & Claypool Publishers ISBN: 161504051X Category : Family & Relationships Languages : en Pages : 221
Book Description
Eggs of all animals contain mRNAs and proteins that are supplied to or deposited in the egg as it develops during oogenesis. These maternal gene products regulate all aspects of oocyte development, and an embryo fully relies on these maternal gene products for all aspects of its early development, including fertilization, transitions between meiotic and mitotic cell cycles, and activation of its own genome. Given the diverse processes required to produce a developmentally competent egg and embryo, it is not surprising that maternal gene products are not only essential for normal embryonic development but also for fertility. This review provides an overview of fundamental aspects of oocyte and early embryonic development and the interference and genetic approaches that have provided access to maternally regulated aspects of vertebrate development. Some of the pathways and molecules highlighted in this review, in particular, Bmps, Wnts, small GTPases, cytoskeletal components, and cell cycle regulators, are well known and are essential regulators of multiple aspects of animal development, including oogenesis, early embryogenesis, organogenesis, and reproductive fitness of the adult animal. Specific examples of developmental processes under maternal control and the essential proteins will be explored in each chapter, and where known conserved aspects or divergent roles for these maternal regulators of early vertebrate development will be discussed throughout this review. Table of Contents: Introduction / Oogenesis: From Germline Stem Cells to Germline Cysts / Oocyte Polarity and the Embryonic Axes: The Balbiani Body, an Ancient Oocyte Asymmetry / Preparing Developmentally Competent Eggs / Egg Activation / Blocking Polyspermy / Cleavage/ Mitosis: Going Multicellular / Maternal-Zygotic Transition / Reprogramming: Epigenetic Modifications and Zygotic Genome Activation / Dorsal-Ventral Axis Formation before Zygotic Genome Activation in Zebrafish and Frogs / Maternal TGF-β and the Dorsal-Ventral Embryonic Axis / Maternal Control After Zygotic Genome Activation / Compensation by Stable Maternal Proteins / Maternal Contributions to Germline Establishment or Maintenance / Perspective / Acknowledgments / References
Author: T.A. Dettlaff Publisher: Springer Science & Business Media ISBN: 1468406825 Category : Science Languages : en Pages : 456
Book Description
Studies of oogenesis occupy an important place in current in vestigations in developmental biology. Today no one has any doubt whatsoever that oogenesis is not just the prelude to development, but is development itself, and a very essential part of it. These words of an eminent Soviet scientist, B. L. As taurov , taken by T. B. Aizenshtadt as an epigraph to her chapter in this book, make a good epigraph for the entire book. It is now clear that during oogenesis not only vast reserves of ribosomes and mitochondria, of yolk, carbohydrates, and lipids, and of enzymes for protein and nucleic acid synthesis and for carbohydrate and fat metabolism (which ensures the energy supply and metabolism of the oocyte and the developing embryo) are formed, but also long-lived mRNA and proteins are synthesized, which determine both the completion of oocyte maturation and the initial stages of embryonic development. In the last 15-20 years, the use of molecular biology methods, electron microscopy, autoradiography, and microsurgical methods of experimental embryology in studying the pre-embryonic development of animals has greatly increased our knowledge of oogenesis. This has led to the need to systematize the data obtained, to reinter pret old ideas, and to review the results obtained by new research trends which have emerged in the last few years and which are of general biological interest. Such a task was undertaken in the book Sovremennye Problemy Oogeneza (Current Problems of Oogenesis), published in 1977 (in Russian).
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: 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: Malgorzata Kloc Publisher: John Wiley & Sons ISBN: 1118492811 Category : Science Languages : en Pages : 459
Book Description
Frogs from the genus Xenopus have long been used as model organisms in basic and biomedical research. These frogs have helped unlock key fundamental developmental and cellular processes that have led to important scientific breakthroughs and have had practical application in embryology, cancer research and regenerative medicine. Xenopus Development is a vital resource on the biology and development of these key model organisms, and will be a great tool to researchers using these frogs in various disciplines of biological science. Xenopus Development is divided into four sections, the first three highlight key processes in Xenopus development from embryo to metamophosis. These sections focus on the cellular processes, organogenesis and embryo development. The final section highlights novel techniques and approaches being used in Xenopus research. Providing thorough and detailed coverage, Xenopus Development, will be a timely and welcome volume for those working in cell and molecular biology, genetics, developmental biology and biomedical research. Provides broad overview of the developmental biology of both Xenopus laevis and Xenopus tropicalis Explores cellular to systems development in key biomedical model organisms Timely synthesis of the field of Xenopus biology Highlights key biomedical and basic biological findings unlocked by Xenopus
Author: Katherine Lee
Author: Katherine Lee
Author: Omar Karl Vieux
Author: Stephen William Eichhorn
Author: Florence Louise Marlow
Author: T.A. Dettlaff
Author: Nahum Sonenberg
Author: 
Author: Bruce Alberts
Author: Malgorzata Kloc
Author: Howard D. Lipshitz