Author: Gun Woo Byeon
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Translation can be critically and pervasively regulated in a transcript-specific manner to modulate protein synthesis. However, it is poorly understood which and how cis-regulatory features of the messenger ribonucleic acid (mRNA) encode variable transcript-specific translation rates to impact spatiotemporal gene expression patterns. Here, I address the role of 5' untranslated (5' UTR) in regulating mRNA translation in vertebrate species. In the first part of the dissertation, I explore the phenomenon of extreme non-coding sequence conservation in vertebrate genomes at the level of RNA function in 5' UTRs. Extreme conservation is a fascinating mystery in comparative genomics in which sequence conservation, at levels often greater than coding regions with invariant polypeptide sequences, stretches on for hundreds of nucleotides in the non-coding regions of the genome. While extreme conservation has been extensively studied for its role in transcriptional regulation, its RNA-level function in translational regulation remains largely unknown. This work reveals the role of extremely conserved 5' UTRs in translational regulation of genes linked to the emergence of essential developmental features in vertebrate species. Extremely conserved 5' UTRs are found to contain cis-elements that promote cell-type specific non-canonical translation initiation. As these elements function as RNA molecules, an understanding of their structures is essential. To this end, I develop in-cell mutate-and-map (icM2), a methodology that maps RNA structure using high-throughput mutational analysis inside cells. icM2 maps the ensemble of multiple conformations in an extremely conserved 5' UTR which is found to be important for its translational regulatory function. I find that active RNA structural remodeling inside cells by RNA helicase activity maintains the relative balance of the conformations. Furthermore, cellular structural remodeling occurs frequently in the most conserved regions of the 5' UTRs. I propose a structural explanation for extreme conservation at the level of RNA and highlight the importance of comparative genomics and of RNA structure in understanding 5' UTR function and evolution. In the second part of the dissertation, I explore the genome-wide role of mammalian ribosome expansion segments (ES) in interacting with 5' UTRs to regulate mRNA translation. ESs are eukaryote-specific insertions to the ribosomal ribonucleic acid (rRNA). They are positioned mostly at the exterior surface of the ribosome structure, extending from the core of the ribosome like flexible tentacles. It has been recently shown that the mammalian ES9S in 18S rRNA directly interacts with a Hox gene 5' UTR element to promote its translation. Direct rRNA-mRNA interaction is not a widely recognized paradigm for translation initiation in eukaryotes. However, addressing the potential genome-wide significance of such a mechanism mediated by ribosome ESs and mRNA 5' UTRs is challenging. Since rRNAs are transcribed from tandem repeats of ribosomal DNA units that can range up to hundreds of thousands of copies, it has not been possible to directly manipulate ESs in most species. To solve this problem, I develop VELCRO-IP RNA-seq: variable expansion segment-ligand chimeric ribosome immunoprecipitation RNA sequencing. VELCRO-IP RNA-seq interrogates the interaction of a ribosome ES with mRNA elements genome-wide by combining yeast genetics, in vitro biochemical pull-down and high-throughput sequencing. By applying VELCRO-IP RNA-seq on mammalian ES9S, hundreds of mRNA regions that interact with the ribosome via specific interaction with the ES are identified. Furthermore, the 5' UTR targets of ES9S are found to promote non-canonical translation. A number of short k-mers that have Watson-Crick complementary to ES9S subsequences are overrepresented in its targets, suggesting potential importance of canonical base-pairing. These results provide evidence for the usage of direct mRNA-rRNA interaction as a mechanism of translation initiation on a wider scale than previously imagined for vertebrate species. Finally, in the last chapter, I discuss how my findings can shape future investigations into the remaining unanswered questions on 5' UTR regulation of translation. Altogether, this dissertation takes us a step closer to the ultimate goal of deciphering the code for translational regulation.
Author: Alfredo Martínez
Publisher: IOS Press
ISBN: 9789051993608
Category : Adrenomedullin
Languages : en
Pages : 410
Get Book Here
Book Description
Adrenomedullin is a recently discovered peptide hormone which involved in many physiological and pathological processes. This book reviews all the information available on this intriguing molecule, covering topics as diverse as blood pressure regulation, growth of tumours and normal cells, the central nervous system, and comparative studies from sharks to mammals. An international group of experts has contributed to this volume which will be of interest to professionals, researchers, and those who will benefit from a broad review of the literature and the main trends in adrenomedullin research.
Author: Lucy W. Barrett
Publisher: Springer Science & Business Media
ISBN: 3034806795
Category : Science
Languages : en
Pages : 63
Get Book Here
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: Erin Margaret Wissink
Publisher:
ISBN:
Category :
Languages : en
Pages : 174
Get Book Here
Book Description
Author: Greco Hernández
Publisher: Springer
ISBN: 3319394681
Category : Science
Languages : en
Pages : 564
Get Book Here
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.
Author: John F. Atkins
Publisher: Springer Science & Business Media
ISBN: 0387893822
Category : Science
Languages : en
Pages : 473
Get Book Here
Book Description
The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.
Author: Nahum Sonenberg
Publisher: CSHL Press
ISBN: 9780879696184
Category : Gene expression
Languages : en
Pages : 1034
Get Book Here
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: Santosh Kumar Upadhyay
Publisher: Academic Press
ISBN: 0128214635
Category : Science
Languages : en
Pages : 392
Get Book Here
Book Description
The growth of human population has increased the demand for improved yield and quality of crops and horticultural plants. However, plant productivity continues to be threatened by stresses such as heat, cold, drought, heavy metals, UV radiations, bacterial and fungal pathogens, and insect pests. Long noncoding RNAs are associated with various developmental pathways, regulatory systems, abiotic and biotic stress responses and signaling, and can provide an alternative strategy for stress management in plants. Long Noncoding RNAs in Plants: Roles in development and stress provides the most recent advances in LncRNAs, including identification, characterization, and their potential applications and uses. Introductory chapters include the basic features and brief history of development of lncRNAs studies in plants. The book then provides the knowledge about the lncRNAs in various important agricultural and horticultural crops such as cereals, legumes, fruits, vegetables, and fiber crop cotton, and their roles and applications in abiotic and biotic stress management. - Includes the latest advances and research in long noncoding RNAs in plants - Provides alternative strategies for abiotic and biotic stress management in horticultural plants and agricultural crops - Focuses on the application and uses of long noncoding RNAs
Author: Ingo Potrykus
Publisher: Springer Science & Business Media
ISBN: 3642792472
Category : Science
Languages : en
Pages : 370
Get Book Here
Book Description
Author: Olga Soutourina
Publisher: Frontiers Media SA
ISBN: 2889765385
Category : Science
Languages : en
Pages : 194
Get Book Here
Book Description
