The Physiological Role of the UPF3 Gene Paralogs in Nonsense-Mediated RNA Decay PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download The Physiological Role of the UPF3 Gene Paralogs in Nonsense-Mediated RNA Decay PDF full book. Access full book title The Physiological Role of the UPF3 Gene Paralogs in Nonsense-Mediated RNA Decay by Eleen Yee Lam Shum. Download full books in PDF and EPUB format.
Author: Eleen Yee Lam Shum
Publisher:
ISBN: 9781321649246
Category :
Languages : en
Pages : 238
Get Book Here
Book Description
Nonsense-mediated RNA Decay (NMD) is a post-transcriptional pathway that degrades aberrant mRNAs, as well as up to ~5% of normal mRNAs. NMD is orchestrated by various factors, including the Upframeshift (UPF) proteins that recognize mRNAs with NMD-inducing features. Of all known factors that participate in NMD, UPF3 is unique in being encoded by two gene paralogs - UPF3A and UPF3B. Loss of UPF3B in humans causes intellectual disability and other neurological disorders. In these patients, as well as other settings in which UPF3B is absent, UPF3A is dramatically upregulated, suggesting that UPF3A compensates for UPF3B. To date, the relationship between these two sister genes and their physiological importance remain elusive.For my dissertation, I elected to study the role of both UPF3A and UPF3B using knockout mouse models. In Upf3b-KO mice, I studied the effect of UPF3B in neuronal development in both the brain and the olfactory epithelium, as well as its downstream effectors in these tissues. I also generated an Upf3a knockout mouse model to study the role of UPF3A in vivo. In the course of my studies, I found that UPF3A, unlike UPF3B, is required for embryonic development. I also discovered that UPF3A is important for spermatogenesis, consistent with the fact that this protein is more highly expressed in the testis than any other adult tissues. Surprisingly, I discovered that while the UPF3A gene is closely related with the UPF3B gene, these two genes have opposing functions. UPF3B promotes NMD, while UPF3A is a NMD inhibitor in several different contexts. Since these two UPF3 proteins are expressed at unequal levels in various tissues, my results suggest that the ratio of these two paralogs dictate the tissue-specific strength of NMD. Together, my research has provided one of the first examples of gene paralogs that have evolved an antagonistic relationship and it has shed light on a unique system to regulate gene expression in a tissue specific and developmentally regulated manner.
Author: Eleen Yee Lam Shum
Publisher:
ISBN: 9781321649246
Category :
Languages : en
Pages : 238
Get Book Here
Book Description
Nonsense-mediated RNA Decay (NMD) is a post-transcriptional pathway that degrades aberrant mRNAs, as well as up to ~5% of normal mRNAs. NMD is orchestrated by various factors, including the Upframeshift (UPF) proteins that recognize mRNAs with NMD-inducing features. Of all known factors that participate in NMD, UPF3 is unique in being encoded by two gene paralogs - UPF3A and UPF3B. Loss of UPF3B in humans causes intellectual disability and other neurological disorders. In these patients, as well as other settings in which UPF3B is absent, UPF3A is dramatically upregulated, suggesting that UPF3A compensates for UPF3B. To date, the relationship between these two sister genes and their physiological importance remain elusive.For my dissertation, I elected to study the role of both UPF3A and UPF3B using knockout mouse models. In Upf3b-KO mice, I studied the effect of UPF3B in neuronal development in both the brain and the olfactory epithelium, as well as its downstream effectors in these tissues. I also generated an Upf3a knockout mouse model to study the role of UPF3A in vivo. In the course of my studies, I found that UPF3A, unlike UPF3B, is required for embryonic development. I also discovered that UPF3A is important for spermatogenesis, consistent with the fact that this protein is more highly expressed in the testis than any other adult tissues. Surprisingly, I discovered that while the UPF3A gene is closely related with the UPF3B gene, these two genes have opposing functions. UPF3B promotes NMD, while UPF3A is a NMD inhibitor in several different contexts. Since these two UPF3 proteins are expressed at unequal levels in various tissues, my results suggest that the ratio of these two paralogs dictate the tissue-specific strength of NMD. Together, my research has provided one of the first examples of gene paralogs that have evolved an antagonistic relationship and it has shed light on a unique system to regulate gene expression in a tissue specific and developmentally regulated manner.
Author: Rita Sattler
Publisher: Springer
ISBN: 331989689X
Category : Medical
Languages : en
Pages : 321
Get Book Here
Book Description
It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Author: Vinay Kumar
Publisher: Springer
ISBN: 3319903187
Category : Science
Languages : en
Pages : 335
Get Book Here
Book Description
Soil salinity is a key abiotic-stress and poses serious threats to crop yields and quality of produce. Owing to the underlying complexity, conventional breeding programs have met with limited success. Even genetic engineering approaches, via transferring/overexpressing a single ‘direct action gene’ per event did not yield optimal results. Nevertheless, the biotechnological advents in last decade coupled with the availability of genomic sequences of major crops and model plants have opened new vistas for understanding salinity-responses and improving salinity tolerance in important glycophytic crops. Our goal is to summarize these findings for those who wish to understand and target the molecular mechanisms for producing salt-tolerant and high-yielding crops. Through this 2-volume book series, we critically assess the potential venues for imparting salt stress tolerance to major crops in the post-genomic era. Accordingly, perspectives on improving crop salinity tolerance by targeting the sensory, ion-transport and signaling mechanisms were presented in Volume 1. Volume 2 now focuses on the potency of post-genomic era tools that include RNAi, genomic intervention, genome editing and systems biology approaches for producing salt tolerant crops.
Author: Torben Heick Jensen
Publisher: Springer Science & Business Media
ISBN: 1441978410
Category : Medical
Languages : en
Pages : 161
Get Book Here
Book Description
The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
Author: Nozomu Mori
Publisher: Springer
ISBN: 4431557636
Category : Medical
Languages : en
Pages : 435
Get Book Here
Book Description
This book brings together the most up-to-date information on recent research results of leading laboratories on aging science in East Asia, particularly in Japan, Korea, and Hong Kong. Starting with a comprehensive overview of various hypotheses on biological mechanisms of aging by Dr. Sataro Goto, each chapter covers broad aspects of the most recent findings in aging-related topics: centenarian studies and genome analysis of progeria, metabolic biochemistry and neurobiology, longevity controls in yeast and nematodes, oxidative stress and calorie restriction, and neurodegeneration mechanisms in Alzheimer’s and Huntington’s diseases, with further potential therapeutic approaches to these age-related neurodegenerative diseases. Also included, in part, is a summary and the outcomes of a scientific discussion forum called the Asian Aging Core for Longevity (AACL) that has been held annually alternating between Japan and Korea during the last decade. This book can serve as a useful resource for finding appropriate collaborators in the areas it covers. The target readership is made up of graduate students and researchers at universities, medical and/or life-science schools, and biomedical and pharmaceutical institutes. Why does aging exist? How do we age? How is each organism’s lifespan determined? These are fundamental questions in the field. We may be still far from achieving a complete view of aging mechanisms, but this book, Aging Mechanisms, offers an excellent opportunity to become familiar with the most updated progress in the biomedical research of aging in Japan and Korea, the two leading nations for human longevity.
Author: Thomas Letzel
Publisher: Royal Society of Chemistry
ISBN: 1849733147
Category : Science
Languages : en
Pages : 195
Get Book Here
Book Description
This book is the first example in presenting LC-MS strategies for the analysis of peptides and proteins with detailed information and hints about the needs and problems described from experts on-the-job. The best advantage is -for sure- the practical insight of experienced analysts into their novel protein analysis techniques. Readers starting in 'Proteomics' should be able to repeat each experiment with own equipment and own protein samples, like clean-up, direct protein analysis, after (online) digest, with modifications and others. Furthermore, the reader will learn more about strategies in protein analysis, like quantitative analysis, industrial standards, functional analysis and more.
Author: Wataru Walter Sutow
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 982
Get Book Here
Book Description
Author: Stanley T. Crooke
Publisher: CRC Press
ISBN: 1439832501
Category : Medical
Languages : en
Pages : 848
Get Book Here
Book Description
Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generati
Author: Milton J. Schlesinger
Publisher: Cold Spring Harbor Laboratory Press
ISBN:
Category : Science
Languages : en
Pages : 218
Get Book Here
Book Description
Author: Lynne E. Maquat
Publisher:
ISBN: 9780429090189
Category : ARN
Languages : en
Pages : 277
Get Book Here
Book Description
Nonsense-Mediated mRNA Decay is the first book devoted to nonsense-mediated mRNA decay (NMD) The rationale for such a book is the enormous information that studies of NMD have provided on the intricacies of post-transcriptional gene expression. The first five sections of the book are divided according to organism and begin with chapters on S. cerevisiae and mammals, from which most NMD data derive. Chapters within these sections discuss the two basic ways cells differentiate between a termination codon that elicits NMD and one that does not. Nonsense-Mediated mRNA Decay makes clear that studies of NMD provide a unique opportunity to examine the coupling of mRNA translation and decay, and relationships between mRNP structure and function. The importance of NMD is evident from descriptions of its influence on the expression of genes that are essential for many cellular processes, including cell differentiation, cell maintenance and cell death. This book is, essentially, meant to be a one-stop source of information that fuels the fires of future experimentation.
