Rozprawy doktorskie: „Post-transcriptional gene regulation”

1

Hayden, Celine. "Post-Transcriptional Gene Regulation in Plants". Diss., Tucson, Arizona : University of Arizona, 2006. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1684%5F1%5Fm.pdf&type=application/pdf.

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Martins, Rute Isabel Paulo. "Post-transcriptional regulation of HFE gene expression". Doctoral thesis, FCT - UNL, 2010. http://hdl.handle.net/10362/5596.

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Thesis presented to obtain the Ph.D. degree in Biology (Molecular Genetics), by the Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia.
O ferro é um elemento essencial em diversos processos metabólicos celulares. O desafio que se coloca para a maioria dos organismos prende-se com o controlo do ferro absorvido de modo a suprir as necessidades destes processos evitando, no entanto, os danos causados pelo ferro livre. Na realidade, algumas das doenças humanas mais comuns estão relacionadas com a perturbação da homeostase do ferro. Entre estas, encontra-se a hemocromatose hereditária que, estando maioritariamente associada a mutações no gene HFE, origina a acumulação de ferro em vários órgãos. A proteína HFE actua na homeostase do ferro através da regulação da expressão da hepcidina no fígado. O principal transcrito HFE apresenta baixos níveis de expressão numa série de tecidos humanos, tendo sido descritos diversos transcritos adicionais. O trabalho aqui apresentado aborda a caracterização dos transcritos alternativos de HFE, os mecanismos envolvidos na sua génese, assim como o seu possível papel fisiológico e regulação. A análise de diversos tecidos humanos permitiu identificar vários transcritos HFE resultantes de splicing alternativo. O estudo funcional de algumas proteínas correspondentes demonstrou que o processo de splicing alternativo pode gerar variantes não funcionais ou produzir uma variante HFE solúvel que é secretada pelas células associada à beta2-microglobulina. Esta proteína poderá desempenhar um papel crucial na homeostase do ferro, actuando como um agonista ou antagonista da HFE full length. Além disso, foi demonstrado que a expressão do transcrito HFE principal é fisiologicamente regulada pelo mecanismo de nonsense-mediated mRNA decay (NMD), dado que os seus níveis aumentam quando este mecanismo é inibido. A pesquisa realizada em tecidos humanos permitiu verificar que a expressão do mRNA HFE resulta da utilização de quatro locais de clivagem e poliadenilação alternativos. Este padrão de poliadenilação alternativa específico de tecido aparenta responder a estímulos de ferro, actuando coordenadamente com o NMD no ajustamento dos níveis de expressão de HFE. Esta dissertação demonstra que a regulação da expressão do gene HFE é influenciada pós-transcricionalmente pelos mecanismos de splicing alternativo, poliadenilação alternativa e NMD. Este conhecimento poderá conduzir a novas perspectivas de investigação na área do metabolismo do ferro e contribuir para o delinear de novas estratégias terapêuticas a aplicar em patologias de homeostase do ferro através da regulação da hepcidina.

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Mavropoulos, Athanasios. "Post-transcriptional regulation of interferon-Î³ gene expression". Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415673.

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Jones, Christopher Iain. "Post-transcriptional gene regulation by the exoribonuclease pacman". Thesis, University of Brighton, 2011. https://research.brighton.ac.uk/en/studentTheses/ff276681-fead-45e4-842f-df0c3a44cfce.

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The gene pacman (pcm) in Drosophila melanogaster encodes the exoribonuclease XRN1, which is highly conserved across eukaryotes and is the only known cytoplasmic exoribonuclease that degrades RNA in the 5’ – 3’ direction. Hypomorphic mutations to pacman have previously been shown cause developmental phenotypes, particularly during wing and thorax development. The focus of this thesis was twofold. Firstly, to create a null pacman allele and associated control lines to further characterise the phenotypes of pcm. Two new alleles were created, one of which was amorphic (pcm14). pcm14 is 100% lethal, and flies die during pupation. The wing imaginal discs of pcm14 larvae are less than half the size of those in wild‐type larvae at the same stage (3rd instar). It was also found that wing imaginal discs in the hypomorphic mutant pcm5 are significantly smaller than wild‐type, by almost 20%. Therefore, pcm appears to play a role in cell proliferation or apoptosis during the growth of wing imaginal discs. Along with pcm14, a new deficiency that includes pcm was created using a DrosDel Rearrangement Screen. The 17,963bp Df(1)ED7452 deficiency is >13 times smaller than the two other publically available deficiencies that include pcm.

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Begbie, Megan Elaine. "Transcriptional and post-transcriptional regulation of the human factor VIII gene". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/NQ45262.pdf.

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Liu, Jun-Li. "Transcriptional and post-transcriptional regulation of somatostatin gene expression by glucocorticoids". Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28826.

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Glucocorticoids and somatostatin both influence a broad spectrum of biological activities and their actions are cooperative in growth control, pancreatic islet function, immune suppression, and stress response, e.g. in vivo studies indicate that glucocorticoids may act through somatostatin to suppress growth, growth hormone secretion and inflammation. Recent studies have suggested that glucocorticoids influence somatostatin production but the precise nature of this effect has remained unclear. In this thesis, I characterized the actions of glucocorticoids on somatostatin gene expression and their molecular mechanisms of action in three consecutive studies. (1) I started with an investigation of the in vivo and in vitro effects of glucocorticoids and found that dexamethasone exerts significant effects on somatostatin peptide and steady state mRNA levels in normal somatostatinoma (1027B$ sb2$) cells. Glucocorticoids stimulate somatostatin production in peripheral tissues (stomach, pancreas, and jejunum) and suppress its biosynthesis in cerebral cortex and hypothalamus. Glucocorticoids induce dose-dependent biphasic effects on steady state somatostatin-mRNA levels in normal rat islet and 1027B$ sb2$ cells, characterized by stimulation at low doses (10$ sp{-10}$ M) and marked inhibition at high doses ($ geq$10$ sp{-7}$ M). This suggests a complex molecular mechanisms of glucocorticoid action on the somatostatin gene involving multi-level regulation. (2) I further discovered that glucocorticoids stimulate somatostatin gene transcription in PC12 (pheochromocytoma) cells transfected with somatostatin promoter-CAT (chloramphenicol acetyl transferase) reporter gene. Dexamethasone induces a dose-dependent 2.2 fold stimulation of somatostatin-CAT expression in PC12 cells and exerts an additive effect on cAMP-induced gene transcription. The dexamethasone effect is abolished in A126-1B2 (protein kinase A-deficient mutant PC12) cells and with CRE (cAMP response element) mutant

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Brown, Naomi Jane. "Post-transcriptional regulation of the pea plastocyanin gene (PetE)". Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597002.

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Expression of the pea plastocyanin gene (PetE) is regulated both by light and by signals from the chloroplast. Previous work has indicated that the light and chloroplast-controlled regulation operates post-transcriptionally in transgenic tobacco, requiring the correct 5’ terminus of the transcript and elements within the plastocyanin-coding region. The post-transcriptional light and chloroplast-controlled regulation of pea PetE has now been demonstrated to operate in transgenic Arabidopsis plants, indicating that the regulation is conserved in an additional plant species. The overall aim of the research described in this dissertation was to investigate the mechanisms by which light and plastid signals influence the stability of PetE transcripts. PetE constructs containing premature stop codons in the coding region were generated to investigate whether translation has a role in the light or chloroplast-controlled regulation. RNA-gel-blot analysis of transgenic plants containing these constructs was used to examine the effects of light and plastid inhibitors on pea PetE transcript accumulation in 7-day-old tobacco seedlings. The results obtained suggested that translation of the start of the PetE coding region is required for both light and plastid-regulated transcript stability. Constructs containing progressive 3’ deletions of the PetE coding region, fused to the Luc reporter gene, were generated to examine how much of the coding sequence is necessary for the regulation. Luciferase assays and RNA-gel-blot analysis were carried out on transgenic tobacco seedlings containing the constructs, to examine the effects of light and plastid inhibitors on the regulation. The results indicated that an element important in the light and chloroplast-controlled regulation is located in the first 12% of the coding region, corresponding to the first 60 nucleotides. The start of the plastocyanin-coding region therefore appears to contain sequences important in the regulation by light and plastid signals, and these sequences may need to be translated in order for the regulation to operate.

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Jia, Tao. "Stochastic Modeling of Gene Expression and Post-transcriptional Regulation". Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/28483.

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Stochasticity is a ubiquitous feature of cellular processes such as gene expression that can give rise to phenotypic differences for genetically identical cells. Understanding how the underlying biochemical reactions give rise to variations in mRNA/protein levels is thus of fundamental importance to diverse cellular processes. Recent technological developments have enabled single-cell measurements of cellular macromolecules which can shed new light on processes underlying gene expression. Correspondingly, there is a need for the development of theoretical tools to quantitatively model stochastic gene expression and its consequences for cellular processes. In this dissertation, we address this need by developing general stochastic models of gene expression. By mapping the system to models analyzed in queueing theory, we derive analytical expressions for the noise in steady-state protein distributions. Furthermore, given that the underlying processes are intrinsically stochastic, cellular regulation must be designed to control the`noise' in order to adapt and respond to changing environments. Another focus of this dissertation is to develop and analyze stochastic models of post-transcription regulation. The analytical solutions of the models proposed provide insight into the effects of different mechanisms of regulation and the role of small RNAs in fine-tunning the noise in gene expression. The results derived can serve as building blocks for future studies focusing on regulation of stochastic gene expression.
Ph. D.

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Rozanska, Agata. "Regulation of post-transcriptional gene expression in human mitochondria". Thesis, University of Newcastle upon Tyne, 2014. http://hdl.handle.net/10443/2706.

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Mitochondria are cellular organelles that have evolved from the eubacterial ancestor into highly specialized compartment of the eukaryotic cell. They are unique among animal cells in that they retain a level of autonomy through the genetic information in their genome. Human mtDNA is built of ~16.5 kbp encoding 13 polypeptides, which are synthesised by mitoribosomes. The latter consist of two RNA species also transcribed from mtDNA and approximately 80 proteins originating from the nucleus. All 13 products of intramitochondrial translation are incorporated into the inner mitochondrial membrane where they co-build the oxidative phosphorylation (OXPHOS) system. OXPHOS is a multicomplex machinery, the final product of which is adenosine triphosphate, ATP, a carrier of energy that is necessary to sustain cell homeostasis and growth. The malfunctions of mitochondria have a severe impact on the ‘host’ organism and are the causative factor in many human diseases. Pathological changes of mitochondrial function can be triggered by mutations in the mitochondrial genome and/or defects in nuclear genes involved in mitochondrial activity. The mitochondrial gene expression pathway has been increasingly investigated during last twenty years and combines both types of factors, those translated in the cytosol and those synthesised in the mitochondrial matrix. A functional mitochondrion requires over 1500 proteins to be imported from the cytosol, a significant subset of these are devoted to the maintenance, replication, transcription and subsequently for translation of the minimal mitochondrial genome fostered within. In the course of my PhD study three of these nuclear encoded but mitochondrially destined proteins were investigated. The first of these proteins that I contributed to investigating was SLIRP. As the specificity of this RNA binding protein had not been established I performed CLIP (cross-linking immunoprecipitation) assay in order to assess the ability of SLIRP to bind RNA. The data generated from this analysis directly showed that SLIRP can interact with all mt-mRNAs apart from MTND6. This work confirmed that SLIRP participates in the stability of mt-mRNA species, as has now been subsequently published by other research groups. A main part of my PhD studies centred on characterisation of MRPL12. This protein belongs to the pool of conserved mitochondrial proteins having the bacterial orthologue 3 called L7/L12. One of the unique features of these proteins is their dynamic character and ability to exchange location between ribosomal LSU and the free pool. This has been postulated to be a regulatory mechanism of translation process in response to fluctuations in cell metabolism. To test this hypothesis I characterised immortalised fibroblasts obtained from a patient with a homozygous mutation in MRPL12 caused by c.542C to T transition in exon 5. This cell line allowed me to study the consequence of this defect on the regulation of translation in human mitochondria. I could conclude that a reduced number of MRPL12 molecules per mt-LSU in subject fibroblasts did not affect overall mitoribosome assembly, but a visible decline in mitochondrial translation was detected although the reduction in translational efficiency for different mitochondrially encoded subunits varied. The third protein that I characterised was mitochondrial RBFA. This protein was identified in my host laboratory and preliminary characterisation performed prior to my involvement. My studies included the CLIP assay that showed direct interaction of this protein with a 3’ terminal stem loop of helix 45 of the 12S mt-rRNA. The methylation status of two conserved neighbouring adenines located in helix 45 was altered by changes in steady state level of RBFA. Moreover, the CLIP data identified a second rRNA species associated with RBFA. This was an unexpected RNA species in the form of 5S rRNA. The data regarding the mitochondrial localisation and specifically any submitochondrial location has been controversial. Intriguingly my data identified a number of chimeric CLIP sequences containing both 5S and 12S rRNA fragments, strongly suggesting that within the mitochondrial matrix RBFA interacts simultaneously with both RNA species. Similarity between the 5S rRNA secondary structure and snoRNA, which guides modifications on cytosolic rRNA, led to the hypothesis proposing a novel function for 5S rRNA guiding methylation at helix 45 of the 12S mtrRNA. My data therefore assign RBFA as a new member of the group of maturation factors of the mammalian mt-SSU.

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Elgamal, Ola A. "TRANSCRIPTIONAL AND POST TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION: APPLICATIONS TO BIOLOGY AND CANCER". The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461071345.

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Panjaworayan, Nattanan, i n/a. "Post-transcriptional regulation of gene expression in Hepatitis B virus". University of Otago. Department of Biochemistry, 2007. http://adt.otago.ac.nz./public/adt-NZDU20071218.143835.

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Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma and liver cirrhosis worldwide. HBV vaccination can prevent new infections, but effective antiviral drugs are not available for a large number of HBV infected patients. To develop novel antiviral drugs, a better understanding of the regulation of HBV gene expression is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNAs from the nucleus of a cell to the site of incorporation into new HBV particles. The HBV post-transcriptional regulatory element (HBV PRE) is a cis acting RNA element found in all HBV transcripts. It has been reported to play an important role in the nuclear export of HBV mRNAs. Moreover, it has the ability to enhance expression of intronless as well as unspliced transcripts. Despite concerted investigations, the functional core element of HBV PRE remains unknown and the exact mechanism of how HBV PRE mediates nuclear export is unclear. This project first produced a complete HBV genome with comprehensive annotation of both coding regions and regulatory signals, which was then used for comparative genomic analysis. The functional elements of the HBV PRE were first subjected to analysis in silico. The HBV PRE is highly conserved among HBVs. Based on this sequence conservation and prediction of conserved RNA secondary structure, potentially functional HBV PRE elements including the previously reported elements (HBV SLα and HBV SLβ) were identified. Experimental deletion analysis of the HBV PRE sequence showed that the effect of each of these elements on the intronless reporter gene�s expression was similar to that of the entire full length HBV PRE. Thus, the results suggested that overall HBV PRE function was not due to additive effects from the individual elements. Surprisingly, a specific sub-section of HBV PRE decreased the level of reporter gene expression. This sub-section has not been identified previously, thus it is a novel HBV PRE inhibitory element. Further analyses using specific reporter assays revealed that the HBV PRE enhanced expression of an unspliced reporter gene whereas the RNA nuclear export elements of retroviruses, CTE (in MPMV) and RRE (in HIV-1) were not able to. Therefore, these results indicate that HBV PRE is involved in inhibition of splicing and it utilizes a different mechanism from CTE and RRE. Interestingly, HBV PRE was observed to be unable to enhance the expression of an intronless luciferase gene. Therefore, HBV PRE is not able to enhance cytoplasmic expression of all intronless transcripts. This project also addressed the idea that the RNA-binding protein, polypyrimidine tract binding protein (PTB) is a positive trans-acting factor for HBV PRE function. Transient expression of exogenous PTB in cultured cells showed no specific effect on constructs containing HBV PRE. Moreover, reduction of endogenous PTB by RNAi did not affect HBV PRE function. Therefore, the results presented in this project do not support the hypothesis that PTB plays a role in HBV PRE function. Given that HBV PRE is highly conserved and present in all HBV transcripts, it makes a good target site for novel molecular therapeutic treatments such as siRNA. To identify potential siRNA target sites within HBV PRE, an RNAi study using a plasmid expressing shRNA against HBV PRE was done. The results from the RNAi study revealed that the expression of a reporter gene could be significantly reduced by siRNA targeted to the HBV PRE. Overall, this project produced a highly annotated HBV genome that can be used as the reference sequence for comparative genomic analysis. Moreover, this work identified novel regulatory elements within HBV PRE that are likely to play an important role in HBV gene expression. Furthermore, the study also identified an excellent siRNA target site within HBV PRE that may inhibit HBV gene expression.

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Jan, Calvin H. "Diverse RNA processing pathways important for post-transcriptional gene regulation". Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/65169.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis. Vita.
Includes bibliographical references.
Cis-acting elements in 3' untranslated regions (UTRs) of mRNAs are crucial to the regulation of gene expression. Animal microRNAs (miRNAs) each target hundreds of mRNAs, which are recognized by pairing to nucleotides 2-7 of the miRNA. MicroRNAs mature through sequential RNase III cleavage of characteristic stem-loop precursors. Cleavage by Drosha defines the premiRNA hairpin, which is then cleaved by Dicer to generate a mature miRNA. This biogenesis pathway ensures high fidelity definition of miRNA 5' ends, which determine target specificity. Small RNAs from Caenorhabditis elegans and Drosophila melanogaster are extensively surveyed here using high-throughput sequencing. Analysis of these libraries led to the discovery of a novel miRNA biogenesis pathway, the mirtron pathway. Unlike canonical miRNAs, mirtrons are defined by intron splicing. The excised intron lariat is debranched and folds into a pre-miRNA hairpin that is cleaved by Dicer. Because of the accuracy of the spliceosome, the mirtron pathway also allows for high fidelity miRNA maturation. The trans-acting siRNAs (tasiRNAs) found in plants also reproducibly generate discrete small RNA species. TasiRNAs align to their parent locus (a TAS gene) in a distinctive 21-nt phase. This phasing is crucial; only siRNAs in the appropriate phase have sufficient complementarity to recognize their targets. The register of this phase is established by miRNA cleavage of the TAS transcript. Analysis of siRNAs sequenced from Physcomitrella patens reveals a conserved pathway in which P. patens TAS genes all possess two cleavage sites for miR390, the miRNA that cleaves TAS3 in Arabidopsis. A second miR390 site was found in Arabidopsis TAS3 that is bound by the miRNA but not cleaved. This interaction is important in triggering tasiRNA production from TAS3 transcripts. A novel approach to mRNA 3' end identification is applied here to determine 3' UTRs in C. elegans. C. elegans UTRs are typically 150 nt long and have a higher density of miRNA seed sites than mammals. Ten percent of genes are alternatively polyadenylated. Approximately 1000 convergent gene pairs were found to use bidirectional poly(A) sites. This architecture maximizes gene density and demonstrates the influence of 3' end formation on the evolution of gene topology.
by Calvin H. Jan.
Ph.D.

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Mayhew, Michael. "Coding regions under non-coding selection: implications for transcriptional and post-transcriptional gene regulation". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21995.

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The signals that facilitate transcriptional and post-transcriptional gene expression regulation are still being understood. Comparative genomics approaches based on the premise that sequence or structure conservation implies functionality have successfully distinguished true regulatory sequences and structures from prediction noise. Protein-coding regions of genes have often been overlooked as potential regulatory sequence regions. A set of 8785 coding region sequences were previously found to be conserved significantly above a baseline protein-coding conservation level. We call these sequences coding regions under non-coding selection or CRUNCS. Analysis of the sequences, the primary contribution of this work, revealed that CRUNCS bases are more often found in coding exon edges and in middle coding exons. CRUNCS-containing genes are more significantly enriched for regulation of transcription and translation, protein ubiquitination, and mRNA processing. CRUNCS are significantly enriched for RNA secondary structure elements. We also uncovered statistical evidence linking CRUNCS to gene splicing regulation.
Les méthodes de génomique comparatives qui sont tirées de la prémisse que la conservation de la séquence ou de la structure implique la conservation de la fonctionnalité, sont parvenues à identifier de vrais signaux régulateurs. Les régions codantes ont souvent été négligées comme des régions potentiellement régulatrices. Un ensemble de 8785 séquences de ces régions plus conservées que prévues a été précédement identifié. L'analyse de ces séquences appelées CRUNCS a révélé que les acides nucléiques des CRUNCS sont plus nombreux aux extrémités des exons et dans les exons centraux. Les gènes contenants des CRUNCS sont enrichis des catégories fonctionnelles comprenant : la régulation de la transcription et la traduction, l'ubiquitination des protéines et le traitement des ARNm. Les CRUNCS sont enrichis d'éléments de structure secondaire de l'ARN. Nous avons aussi découvert des preuves statistiques démontrant que les CRUNCS jouent un rôle dans la régulation de l'épissage des gènes.

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Almlöf, Tova. "Gene regulation by the glucocorticoid receptor : post-DNA binding mechanisms of transcriptional activation /". Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2675-1.

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Janga, Sarath Chandra. "Exploiting network-based approaches for understanding gene regulation and function". Thesis, University of Cambridge, 2010. https://www.repository.cam.ac.uk/handle/1810/236171.

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It is increasingly becoming clear in the post-genomic era that proteins in a cell do not work in isolation but rather work in the context of other proteins and cellular entities during their life time. This has lead to the notion that cellular components can be visualized as wiring diagrams composed of different molecules like proteins, DNA, RNA and metabolites. These systems-approaches for quantitatively and qualitatively studying the dynamic biological systems have provided us unprecedented insights at varying levels of detail into the cellular organization and the interplay between different processes. The work in this thesis attempts to use these systems or network-based approaches to understand the design principles governing different cellular processes and to elucidate the functional and evolutionary consequences of the observed principles. Chapter 1 is an introduction to the concepts of networks and graph theory summarizing the various properties which are frequently studied in biological networks along with an overview of different kinds of cellular networks that are amenable for graph-theoretical analysis, emphasizing in particular on transcriptional, post-transcriptional and functional networks. In Chapter 2, I address the questions, how and why are genes organized on a particular fashion on bacterial genomes and what are the constraints bacterial transcriptional regulatory networks impose on their genomic organization. I then extend this one step further to unravel the constraints imposed on the network of TF-TF interactions and relate it to the numerous phenotypes they can impart to growing bacterial populations. Chapter 3 presents an overview of our current understanding of eukaryotic gene regulation at different levels and then shows evidence for the existence of a higher-order organization of genes across and within chromosomes that is constrained by transcriptional regulation. The results emphasize that specific organization of genes across and within chromosomes that allowed for efficient control of transcription within the nuclear space has been selected during evolution. Chapter 4 first summarizes different computational approaches for inferring the function of uncharacterized genes and then discusses network-based approaches currently employed for predicting function. I then present an overview of a recent high-throughput study performed to provide a 'systems-wide' functional blueprint of the bacterial model, Escherichia coli K-12, with insights into the biological and evolutionary significance of previously uncharacterized proteins. In Chapter 5, I focus on post-transcriptional regulatory networks formed by RBPs. I discuss the sequence attributes and functional processes associated with RBPs, methods used for the construction of the networks formed by them and finally examine the structure and dynamics of these networks based on recent publicly available data. The results obtained here show that RBPs exhibit distinct gene expression dynamics compared to other class of proteins in a eukaryotic cell. Chapter 6 provides a summary of the important aspects of the findings presented in this thesis and their practical implications. Overall, this dissertation presents a framework which can be exploited for the investigation of interactions between different cellular entities to understand biological processes at different levels of resolution.

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Söderberg, Malin. "Post-Transcriptional Regulation of the Murine Inducible Nitric Oxide Synthase Gene". Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6137.

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Large amounts of nitric oxide (NO) are produced by the inducible nitric oxide synthase (iNOS) upon inflammatory stimuli. NO is a multifaceted molecule, which may have beneficial effects as an antimicrobial agent in the immune defense, or cytotoxic effects in chronic inflammations, manifested as e.g. arthritis and asthma. Understanding the mode of regulation of the iNOS gene is a prerequisite for developing intervention strategies in various pathological conditions where detrimental effects of NO need to be prevented.

Transcriptional processes of the iNOS gene regulation are well described, while post-transcriptional events have not been studied in detail. The aim of the present thesis was to investigate post-transcriptional regulatory mechanisms involving the 3’untranslated region (UTR) of the murine iNOS mRNA.

Inflammation-dependent RNA-protein interactions with the iNOS mRNA 3’UTR were characterized by RNA gel shift analysis and UV cross-linking. Trans-acting factors interacting with the 3’UTR were detected in mouse liver and macrophages and identified as heterogeneous nuclear ribonucleoproteins (hnRNP) I and L. Western blot revealed that reduced hnRNPI levels are responsible for the decreased interaction of hnRNPI with iNOS 3’UTR upon induction in inflammatory conditions. This decrease was reversed by the glucocorticoid dexamethasone, concomitant with decreased iNOS mRNA levels and stability. Introduction of the iNOS 3’UTR into a luciferase reporter gene reduced its expression in macrophages. Upon deletions of the binding sites for hnRNPI and hnRNPL, the luciferase expression was recovered. In addition, inflammatory stimuli increased the luciferase activity of the construct with the full-length 3’UTR, while only weak effects of the stimuli were seen on the deletion constructs.

In conclusion, the results suggest that binding of hnRNPI and hnRNPL to the iNOS mRNA 3’UTR promotes degradation of the transcript. Induction of iNOS by inflammatory stimuli dissociates the RNA-protein complex, yielding a more stable mRNA. In addition, post-transcriptional down-regulation of the iNOS gene by the anti-inflammatory glucocorticoid dexamethasone, seems to involve hnRNPI.

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Söderberg, Malin. "Post-transcriptional regulation of the murine inducible nitric oxide synthase gene /". Uppsala : Acta Universitatis Upsaliensis: Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6137.

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Preiss, Thomas. "Cytochrome c oxidase : a model system for post-transcriptional gene regulation". Thesis, University of Newcastle Upon Tyne, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281705.

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Allen, Margaret Louise. "Post-transcriptional regulation of expression of the potassium channel, Kv1.1 /". Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/6264.

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Lawler, Katherine Joanne. "Transcriptional and post-transcriptional regulation of gene expression : computational analysis of microarray studies in fungal species". Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608593.

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Sawicka, Kirsty J. "Post-transcriptional regulation of gene expression by the polypyrimidine tract binding protein". Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537674.

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Diaz, Manisha Regina. "Regulation of virulence gene expression by Rsm homologs in Pseudomonas aeruginosa". Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4612.

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Pseudomonas aeruginosa RsmA belongs to the CsrA family of RNA binding proteins. CsrA family members are post-transcriptional regulators of global gene expression and usually function to inhibit translation of target genes, but in some cases can also exert positive regulatory effects. Previous work from our lab determined that RsmA is required for maximal T3SS gene expression in P. aeruginosa strain PA103. Nevertheless, the molecular mechanism underlying the RsmA-mediated control of T3SS gene expression was unknown. Expression of the T3SS is under the direct control of ExsA, a transcriptional activator. Previous microarray analyses showed that exsA transcript levels were reduced two-fold in an rsmA mutant. In chapter II I examine the role of RsmA in regulating ExsA expression. I demonstrate that expression of a ExsA-LacZ translational fusion was reduced two-fold in an rsmA mutant suggesting a specific effect of RsmA on ExsA expression. The effect of RsmA on ExsA expression occurs at a post-transcriptional level and is independent of mRNA and protein stabilization mechanisms. RsmA directly interacts with the exsCEBA transcript at multiple sites. Truncation analyses indicate that the -37 to +85 region (relative to the ATG start codon) is necessary and sufficient for RsmA-dependent control. I identified two binding sites, BS1 (-25 bp) and BS2 (+84), involved in the interaction of RsmA with the exsA transcript using sequence analysis, site-directed mutagenesis, EMSA assays, RNase footprints, and RNaseH cleavage assays. Mutagenesis of both binding sites results in an RsmA-independent phenotype. I further demonstrate that RsmA is able to activate ExsA expression. I propose a model wherein RsmA relieves a block on ExsA translation. Collectively, this work shows that RsmA directly binds and activates ExsA expression at the post-transcriptional level. Most Pseudomonas species carry at least two homologs of CsrA on the chromosome, but only one copy had been identified in P. aeruginosa. Through the course of other projects in the lab, we observed several phenotypes that could not be accounted for by a single copy of RsmA. In collaboration with the Wolfgang lab, we identified a second CsrA homolog, RsmF in P. aeruginosa. RsmF is dimeric in solution. The structure of RsmF differs substantially from other CsrA homologs by having alpha-helices located between the beta-2 and beta-3 strands. In chapter III I examine the role of RsmF in regulating RsmA-controlled processes associated with acute (T3SS) and chronic (T6SS and biofilm formation) infection. I discovered that while an rsmF mutant alone does not exhibit a phenotype, simultaneous deletion of both rsmA and rsmF significantly accentuates the phenotypes exhibited by an rsmA mutant alone. I show that RsmA directly binds and represses RsmF translation and that the small regulatory RNAs RsmZ and RsmY do not significantly modulate RsmF activity. Site-directed mutagenesis revealed that Arg 62, located in the beta-1 and beta-5 fold, is essential for biological activity in vivo and RNA-binding in vitro suggesting a conserved mechanism of RNA recognition maintained across all CsrA family members. Finally, I show that RsmF binds to only a subset of RsmA targets and is not involved in the regulation of all RsmA-controlled processes. In chapter IV I identified high-affinity RNA ligands from a chemically synthesized oligonucleotide library using systematic evolution of ligands by exponential enrichment (SELEX) and high-througput sequencing. From preliminary analyses of high-throughput sequencing data, the RsmF-binding consensus was determined as 5'-RUACARGGAC-3', with the ARGGA motif being 95% conserved. Collectively, this work shows that Rsm homologs play important roles in regulating virulence gene expression in P. aeruginosa.

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Richardson, Jonathan Paul. "Post-transcriptional regulation of gene expression by the (PSI) prion of Saccharomyces cerevisiae". Thesis, University of Aberdeen, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395144.

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Termination of protein synthesis in the yeast Saccharomyces cerevisiae occurs when the eukaryotic release factor eRF1 recognises the stop codon. The rate of termination is enhanced by a second release factor, eRF3 (a GTPase). The efficiency of stop codon recognition by eRF1 is influenced by the surrounding nucleotide context of the stop codon, and in yeast, by the structural properties of eRF3, which displays prion-like characteristics. eRF3 in the [PSI⁺], prion state forms insoluble high molecular weight aggregates that cause inefficient termination (nonsense suppression). This study tested the hypothesis that the [PSI⁺] state may direct suppression of stop codons, particularly those in weak contexts. This may confer unique phenotypes upon yeast, particularly stress response phenotypes, caused by C-terminal extension of a subset of proteins. Consistent with this hypothesis, the [PSI⁺] state was found to enhance suppression of all stop codons, with those in weak contexts being most efficiently suppressed. [PSI] is thus a context sensitive suppressor of all three stop codons. Using computer screening, yeast genes whose open reading frames terminate in weak nucleotide contexts were identified as potential candidates for [PSI⁺]-directed stop codon readthrough.

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24

Warner, Matthew John. "Mechanisms of post-transcriptional gene regulation in the developmental programming of adulthood disease". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610291.

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Peterson, Maureen. "Transposon Regulation: Control of Expression in Drosophila Melanogaster and Consequences of Disregulation in Human Cells". Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/203469.

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Transposons were first discovered as "jumping genes" by Barbara McClintock, who continued to study them in maize through the 1940's and 1950's. Since then, transposons have been shown to make up a large percentage of eukaryotic genomes, including close to half of the human genome, but have been dismissed as simply "junk DNA." Recently, the importance of keeping transposons tightly regulated within the cellular environment has begun to be appreciated; the mechanisms to accomplish this have been studied and the current understanding of pathways governing transposon regulation is discussed within this dissertation. However, recent work presented within the scope of this dissertation in Drosophila melanogaster revealed a previously unknown function for condensin complexes in transposable element regulation. These studies provide a link between pathways governing chromosome pairing and transposon regulation. The potential interplay between these two pathways is intriguing and until now, largely unexplored.Aside from how transposons themselves are regulated, studies into potential roles they may play in the regulation of other protein coding genes within the cell may provide clues into the functionality of these elements within our genome. As a specific example, BRCA1 has a high density of retrotransposon sequences within its primary transcript, and studies of BRCA1 regulation presented within this dissertation has led to the development of a model for a novel gene regulatory mechanism occurring in human cells involving retrotransposons. This mechanism may provide direct relevance to cancer etiology, as retrotransposons have long been known to be misregulated in cancer.As a sum, the work presented within this dissertation extends our knowledge of how transposons are regulated and provides some of the first evidence for their functionality in gene regulatory pathways within human cells.

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26

Yaman, Ibrahim. "Mechanisms of Post-transcriptional Regulation of Cat-1 Gene Expression by Amino Acid Starvation". Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1120145927.

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Oberstrass, Florian Christophe. "Novel modes of protein-RNA recognition in post-transcriptional gene regulation studied by NMR spectroscopy". kostenfrei kostenfrei, 2007. http://e-collection.ethbib.ethz.ch/view/eth:30123.

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Ciriello, Simona [Verfasser], i Niels H. [Akademischer Betreuer] Gehring. "Separate functions of BTZ during post-transcriptional gene regulation / Simona Ciriello. Gutachter: Niels H. Gehring". Köln : Universitäts- und Stadtbibliothek Köln, 2014. http://d-nb.info/1069985805/34.

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Cheng, Wu Albert. "Epigenetic and post-transcriptional regulation of gene expression in pluripotent stem cells, differentiation and metastasis". Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/91122.

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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2014.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Transmission of information from DNA to RNA to protein underlies the core of modem life forms. The advance in sequencing and genetic technologies has revolutionized the study of molecular biology, genetics and developmental biology enabling delineation of biological processes in unprecedented details. Through the study of epigenetics and posttranscriptional regulation of gene expression by high-throughput sequencing technologies in several biological processes, namely embryonic stem cells, somatic reprogramming, erythroid differentiation, epithelial-mesenchymal transition and cancer metastasis, this thesis work has identified novel players and regulatory mechanisms underlying these developmental processes and diseases. Furthermore, an attempt to engineer CRISPRzymes - protein fusions of RNA-guided DNA binding dCas9 - will enable experiments to directly test biological processes at defined genomic loci and expands the toolbox for synthetic biology and potentially opens up opportunities for novel therapeutics.
by Wu Albert Cheng.
Ph. D.

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30

Deveau, Laura M. "Characterizing the Disorder in Tristetraprolin and its Contribution to Post-Transcriptional Gene Regulation: A Dissertation". eScholarship@UMMS, 2016. http://escholarship.umassmed.edu/gsbs_diss/855.

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RNA-binding proteins (RBPs) are important for a wide variety of biological processes involved in gene regulation. However, the structural and dynamic contributions to their biological activity are poorly understood. The tristetraprolin (TTP) family of RBPs, including TTP, TIS11b and TIS11d, regulate the stability of mRNA transcripts encoding for key cancer-related proteins, such as tumor necrosis factor- and vascular endothelial growth factor. Biophysical studies have shown that the RNA binding domain, consisting of two CCCH zinc fingers (ZFs), is folded in the absence of RNA in TIS11d and TIS11b. In TTP, however, only ZF1 adopts a stable fold, while RNA is required to completely fold the tandem zinc finger (TZF). The focus of this research was to understand the origin and biological significance of the structural differences observed for the TZF domains of TTP and TIS11d. Three residues were shown to control the affinity for the structural Zn2+ and determine the folding of ZF2 in the absence of RNA. The partially-folded TZF domain of TTP has greater selectivity for RNA sequences than the fully folded TZF domain of TIS11d. The mRNA destabilizing activity of TTP was increased when the partially disordered RBD of TTP was replaced with the fully structured TZF domain of TIS11d. Disruption of the structure and/or dynamics of the TZF domain observed in the disease-associated mutations of TIS11d, P190L and D219E, results in aberrant cytoplasmic localization. This work demonstrates that the extent of RBD folding in the TTP family is important for differential RNA recognition, mRNA turnover, and protein localization in vivo.

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31

Miller, Ian, i Christopher Pritchett. "A Stem-Loop Secondary Structure Influencing Expression Of The Post-Transcriptional Regulator, RsmA, In Pseudomonas aeruginosa". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/76.

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Pseudomonas aeruginosa is an infectious Gram-negative bacillus that is found in environments ranging from aerobic to anaerobic, soil to water, plant tissues to human tissues, and even found thriving on plastics and medical implant devices. P. aeruginosa is a major concern for individuals who have cystic fibrosis, chronic obstructive pulmonary disorder, diabetes, have recently undergone surgery, have recently experienced severe burns, or have experienced other ailments that resulted in a compromised immune system, such as Human Immunodeficiency Virus (HIV). P. aeruginosa evades the host immune response by expressing a myriad of virulence factors, and it is through stringent gene regulation of virulence factors that allow P. aeruginosa to initiate acute infections and persist as a chronic infection of its host. The expression of virulence factors is controlled by a complex regulatory system comprised of Two-Component Systems (TCS), post-transcriptional regulators, small non-coding RNAs (sRNA), and others. A significant post-transcriptional regulator involved in this regulatory network is the Regulator of Secondary Metabolites (RsmA). RsmA belongs to the CsrA family of mRNA binding proteins found in many Gram-negative bacteria. Much is known about the targets of RsmA and its functions; however, little is known about how RsmA itself is regulated. Leader sequences, 5’ and 3’, have been demonstrated to have regulatory roles. Using bioinformatics, we have observed potential for the formation of a stem-loop secondary structure in the 5’ leader sequence of rsmA. We propose that this stem-loop plays an important role in the expression of RsmA in P. aeruginosa. In this study, we constructed rsmA leader fusions using the lacUV5 promoter and lacZ reporter to measure translation with and without the secondary structure present. Secondly, we introduced point mutations in the stem of the stem-loop of the leader fusions to disrupt the formation of the stem-loop. Finally, we performed Site-Directed Mutagenesis on the rsmA leader to examine protein levels in vivo via western blot analysis using an HA-tagged rsmA. Our data shows that when the stem-loop formation is disrupted or deleted, translation of RsmA increases. This data suggests that the stem-loop provides a regulatory function in the expression of RsmA.

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32

Rehage, Nina Beate [Verfasser], i Vigo [Akademischer Betreuer] Heissmeyer. "Screening for cofactors in Roquin-mediated post-transcriptional gene regulation / Nina Beate Rehage ; Betreuer: Vigo Heissmeyer". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/114485752X/34.

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Victor, Xylophone Vijai Aasee. "Angiotensin II-mediated Regulation of the Human Angiotensin II Type 1 Receptor Gene". Diss., CLICK HERE for online access, 2005. http://contentdm.lib.byu.edu/ETD/image/etd952.pdf.

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Carlile, Mark. "Post-transcriptional regulation of the npt2-gene locus in Zebrafish and mouse by a natural antisense transcript". Thesis, University of Newcastle upon Tyne, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506431.

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35

Rapone, Roberta. "Essential cytoplasmic role(s) of the histone lysine methyltransferase Setdb1 in post-transcriptional regulation of gene expression". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/RAPONE_Roberta_va.pdf.

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Setdb1 est une «histone» lysine méthyltransférase (KMT) appartenant à la famille SUV39, l’une des principales machineries épigénétiques de répression des gènes. Setdb1 établit notamment la mono-, la di- et la tri- méthylation sur la lysine 9 de l'histone H3 (H3K9).Setdb1 est essentiel pour la survie, la pluripotence et l'auto-renouvellement des cellules souches embryonnaires de souris (mESCs); son knock-out est mortel au stade de la péri-implantation à 3,5 dpc chez la souris. Setdb1 est également nécessaire pour la différenciation de nombreux types de cellules progénitrices : spermatogenèse, neurogenèse, différenciation des chondrocytes et différenciation des muscles squelettiques. De plus, Setdb1 a été associé à plusieurs maladies: il est amplifié dans le mélanome et le cancer du poumon et il est dérégulé dans les cancers du foie, de la prostate, colorectal et du sein, dans la maladie de Huntington et la schizophrénie. Remarquablement, au-delà des histones, Setdb1 méthyle nombreux substrats non-histones, y compris UBF, p53, Akt, Tat et Ing2.Bien que Setdb1 ait toujours été associé à son rôle nucléaire, il s'avère que Setdb1 est la seule KMT de la famille SUV39 à avoir également une localisation cytoplasmique, dans plusieurs types de cellules, y compris les mESCs, les fibroblastes embryonnaires de souris (MEFs) et les cellules HeLa. Cependant, la fonction de Setdb1 dans le cytoplasme reste totalement inconnue. Pour étudier le rôle cytoplasmique de Setdb1, nous avons utilisé des cellules souches embryonnaires de souris (mESCs), dans lesquelles Setdb1 est essentiel. Nos résultats montrent que Setdb1 cytoplasmique est crucial pour la survie des mESCs: en effet, le nombre de cellules apoptotiques augmente après la perte de Setdb1 cytoplasmique. Nous avons constaté que le Setdb1 cytoplasmique affecte la synthèse de protéines dans les mESCs. Nous montrons en outre que le Setdb1 cytoplasmique interagit avec la protéine Trim71 spécifique de mESC (également appelée Lin41) et avec le facteur de traduction d'initiation eIF3c dans les mESC. Enfin, nous avons démontré que Setdb1 et Trim71 co-régulent ensemble la stabilité et la traduction des mARNs. Nos données actuelles mettent au jour la fonction cytoplasmique essentielle d'une lysine méthyltransférase appelée Setdb1, au début considérée comme étant spécifique uniquement des histones et apportent de nouvelles informations sur la régulation post-transcriptionnelle de l'expression génique médiée par un régulateur épigénétique fondamental
Setdb1 is a “histone” lysine methyltransferase (KMT) belonging to the SUV39 family that methylates lysine 9 of histone H3 (H3K9), one of the major epigenetic machineries mainly involved in gene repression. Notably, Setdb1 establishes mono-, di- and tri-methylation of H3K9. Setdb1, or Eset in mice, is essential for the survival, the pluripotency and the self-renewal of mouse embryonic stem cells (mESCs); Eset knockout is lethal at the peri-implantation stage at 3.5 dpc in mice. Setdb1 is also required for the differentiation of many progenitor cell types: spermatogenesis, neurogenesis, chondrocyte differentiation and skeletal muscle differentiation. Moreover, Setdb1 has been associated with several diseases: it is amplified in melanoma and lung cancer and it is dysregulated in liver, prostate, colorectal and breast cancers, Huntington disease and schizophrenia.Remarkably, beyond histones, Setdb1 methylates many non-histone substrates, such as UBF, p53, AKT, Tat and ING2 proteins. Although Setdb1 has been always associated with its nuclear role, it turns out that Setdb1 is the only H3K9 KMT to have also a cytoplasmic localization, in several cell types, including mESCs, mouse embryonic fibroblasts (MEFs) and HeLa cells. However, the function of Setdb1 in the cytoplasm remains totally unknown. To investigate Setdb1 cytoplasmic role, we have used mouse embryonic stem cells (mESCs), in which Setdb1 is essential. Our results show that cytoplasmic Setdb1 is crucial for the survival of mESCs: indeed, the number of apoptotic cells increases after the loss of cytoplasmic Setdb1. We found that cytoplasmic Setdb1 affects newly protein synthesis in mESCs. We further show that cytoplasmic Setdb1 interacts with mESCs-specific protein Trim71 (also called Lin41) and with the initiation translation factor eIF3c in mESCs. Finally, we reported that Setdb1 and Trim71 together co-regulate mRNA stability and translation. Our current data unravel the essential cytoplasmic function of Setdb1, for long time considered exclusively an “histone” lysine methyltransferase, and provide new insights into the post-transcriptional regulation of gene expression mediated by a fundamental epigenetic regulator

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36

Leung, Tsz-ki, i 梁子騏. "Transcriptional and post-translational regulations of junctional adhesion molecule-c in mouse germ cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43571992.

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Paul, Priyanka. "TRANSCRIPTIONAL AND POST-TRANSLATIONAL REGULATION OF TERPENOID INDOLE ALKALOID BIOSYNTHESIS IN CATHARANTHUS ROSEUS". UKnowledge, 2017. http://uknowledge.uky.edu/pss_etds/94.

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Catharanthus roseus (Madagascar periwinkle) is the exclusive source of an array of terpenoid indole alkaloids (TIAs) that are used in the treatments of hypertension and certain types of cancer. TIA biosynthesis is under stringent spatiotemporal control and is induced by jasmonate (JA) and fungal elicitors. Tryptamine, derived from the indole branch, and secologanin from the iridoid branch are condensed to form the first TIA, strictosidine. Biosynthesis of TIA is regulated at the transcriptional level and several transcription factors (TFs) regulating the expression of genes encoding key enzymes in the pathway have been isolated and characterized. The JA-responsive APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF), ORCA3, and the basic helix-loop-helix (bHLH) factor, CrMYC2, are the key activators of the TIA biosynthesis. Recently, two other TFs, the bHLH IRIDOID SYNTHESIS 1 (BIS1) and BIS2 were also identified as regulators of TIA pathway. Analysis of C. roseus genome sequence has revealed that ORCA3 forms a physical cluster with two uncharacterized AP2/ERFs, ORCA4 and ORCA5. In plants, physically linked clusters of TFs are less characterized. Moreover, the regulation of TF clusters is relatively unexplored. My research uncovered that the ORCA gene cluster is differentially regulated. ORCA4 and ORCA5, while functionally overlapping with ORCA3, regulate an additional set of TIA pathway genes. ORCA4 or ORCA5 overexpression has resulted in significant increase of TIA accumulation in C. roseus hairy roots. In addition, ORCA5 directly regulates the expression of ORCA4 and indirectly regulates ORCA3, likely via unknown factor(s). Interestingly, ORCA5 also activates the expression of ZCT3, a negative regulator of the TIA pathway. In addition CrMYC2 is capable of activating ORCA3 and co-regulating pathway genes concomitantly with ORCA3. Several lines of evidence suggest that, in addition to the transcriptional control, biosynthesis of TIAs is also controlled at the posttranslational level, such as protein phosphorylation. Available literature indicates that a mitogen-activated protein kinase (MAPK) cascade is involved in this process. Analysis of C. roseus MAP kinome, identified two independent MAPK cascades regulating the indole and iridoid branches of the TIA pathway. We showed that the ORCA cluster and CrMYC2 act downstream of a MAP kinase cascade consisting of CrMAPKK1, CrMAPK3 and CrMAPK6. Overexpression of CrMAPKK1 in C. roseus hairy roots upregulates TIA pathway genes expressions and boosts TIA accumulation. The other cascade, consisting of CrMAPKK6 and CrMAPK13, mostly regulates the iridoid branch of the TIA pathway. Overexpression of CrMAPK13 in C. roseus hairy roots significantly upregulates iridoid pathway genes and boosts tabersonine accumulation. Moreover, we recently identified the third MAPK cascade, consisting of CrMAPKK1 and CrMAPK20, that negatively regulates the indole branch of the TIA pathway. Overexpression of CrMAPK20 in C. roseus hairy roots represses the genes regulated by CrMYC2-ORCAs and reduces catharanthine accumulation. These findings significantly advance our understanding of transcriptional and post-translational regulatory mechanisms that govern TIA biosynthesis in C. roseus.

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Boland, Andreas [Verfasser], i Thilo [Akademischer Betreuer] Stehle. "Structural characterization of eukaryotic mRNA decay factors involved in post-transcriptional gene regulation / Andreas Boland ; Betreuer: Thilo Stehle". Tübingen : Universitätsbibliothek Tübingen, 2014. http://d-nb.info/1163235474/34.

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Jeltsch, Katharina [Verfasser], i Daniel [Akademischer Betreuer] Krappmann. "Role of post-transcriptional gene regulation by Roquin in T cell activation and differentiation / Katharina Jeltsch. Betreuer: Daniel Krappmann". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1082504866/34.

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Kronbeck, Nina Isabella [Verfasser], i Vigo [Akademischer Betreuer] Heissmeyer. "Analyzing cooperative post-transcriptional gene regulation by Roquin in the prevention of autoimmunity / Nina Isabella Kronbeck ; Betreuer: Vigo Heissmeyer". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1216039151/34.

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McCue, Andrea D. "Transposable element RNAi goes beyond post-transcriptional silencing: mRNA-derived small RNAs both regulate genes and initiate DNA methylation". The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437481732.

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Moore, Jocelyn. "Post-transcriptional control of Drosophila pole plasm component, germ cell-less". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115700.

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Mechanisms of post-transcriptional control are critical to deploy RNAs and proteins asymmetrically to a discrete region of cytoplasm at the posterior of the Drosophila oocyte and embryo, called the pole plasm and thus allow differentiation of the germline. Research presented in this thesis investigates the post-transcriptional control of Drosophila pole plasm component germ cell-less (gcl ). Maternal gcl activity is required for germ cell specification and gcl RNA and protein accumulate asymmetrically in the pole plasm. gcl RNA, but not Gcl protein, is also detected in somatic regions of the embryo, and ectopic expression of Gcl in the soma causes repression of somatic patterning genes suggesting that gcl RNA is subject to translational control. I find that Gcl is expressed during oogenesis, where its expression is regulated by translational repressor Bruno (Bru). Increased levels of Gcl are observed in the oocyte when Bru is reduced (i.e., in an arrest heterozygote) and Bru overexpression reduces the amount of Gcl. Consistent with this, reduction of the maternal dosage of Bru leads to ectopic Gcl expression in the embryo, which, in turn, causes repression of anterior huckebein RNA expression. Bruno binds directly to the gcl3'UTR in vitro, but surprisingly, this binding is largely independent of a Bruno Response Element (BRE) in the gcl 3'UTR and depends upon a novel site. Furthermore, the gcl BRE-like region is not required to repress Gcl expression during oogenesis or embryogenesis. I concluded that Bru regulates gcl translation in a BRE-independent manner. In addition, I established the role of the gcl 3'UTR in gcl RNA localization and translation using transgenes that replace the endogenous 3'UTR with the alpha-tubulin 3'UTR or place it in tandem to the bicoid 3'UTR. I find that accumulation of gcl RNA in the embryonic pole plasm requires the gcl 3'UTR. Moreover, Gel is restricted to the pole plasm by translational repression mediated by the gcl 3'UTR and a limiting pool of trans-acting translational repressors. The phenotypic consequences of loss of this translational control are relatively mild, suggesting that gcl translation does not require stringent repression in the soma.

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Alvarez-Saavedra, Matias Alberto. "MicroRNA-132-Dependent Post-Transcriptional Regulation of Clock Entrainment Physiology Via Modulation of Chromatin Remodeling and Translational Control Gene Targets". Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28722.

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Mammalian circadian rhythms of behaviour are synchronized to external time by daily resetting of the master pacemaker, the suprachiasmatic nucleus (SCN), in response to light, in a process known as light-induced clock entrainment. microRNA-132 (miR-132) is induced by light within the SCN via a MAPK-CREB-dependent mechanism and has the capacity to attenuate the entraining effects of light. However, the identity of the genes that miR-132 regulates and their roles in the light-entrainment process have not yet been characterized. This thesis describes that 2 gene clusters involved in chromatin remodeling (i.e. Mecp2, Ep300, Jarid1a) and translational control (i.e. Btg2, Paip2a) are under the regulation of miR-132 in the SCN and coordinated regulation of these genes underlies miR132-dependent modulation of mPeriod1 (mPer1) and mPeriod2 (mPer2) and the light-entrainment process. I find that the Period genes are bound and transcriptionally modulated by MeCP2. In addition, Paip2a acts as a repressor of Period translation. This work further proposes that miR-132 is enriched for chromatin and translation-associated target genes-and, thus, miR-132 is an important orchestrator of chromatin remodeling and protein translation within the SCN clock, thereby fine-tuning clock entrainment.

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Natalin, Pavel. "Post-transcriptional gene regulation in Drosophila an investigation into the roles of RNA silencing and the DEAD-box helicase Belle /". [S.l. : s.n.], 2009. http://nbn-resolving.de/urn:nbn:de:bsz:16-opus-89391.

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Duggimpudi, Sujitha Smruthy [Verfasser]. "Elucidating the physiological function of the RNA binding protein EWS and its role in post-transcriptional gene regulation / Sujitha Smruthy Duggimpudi". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2015. http://d-nb.info/1080298142/34.

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Mohamed, Farida Y. "The mechanism(s) of post-transcriptional regulation of the human constitutive endothelial nitric oxide synthase gene by tumor necrosis factor-alpha". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0014/NQ59215.pdf.

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Zagore, Leah Louise. "The Molecular Function of the RNA Binding Protein DAZL in Male Germ Cell Survival". Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1575647143675768.

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Sweet, Thomas Jeffrey. "New Insights Into the Relationship Between Messenger RNA Translation and Degradation". Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1321298653.

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Hallal, Samantha. "Characterisation of the zinc fingers of Erythroid Kruppel-Like Factor". Thesis, The University of Sydney, 2008. http://hdl.handle.net/2123/4030.

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Gene expression is known to be regulated at the level of transcription. Recently, however, there has been a growing realisation of the importance of gene regulation at the post-transcriptional level, namely at the level of pre-mRNA processing (5’ capping, splicing and polyadenylation), nuclear export, mRNA localisation and translation. Erythroid krüppel-like factor (Eklf) is the founding member of the Krüppel-like factor (Klf) family of transcription factors and plays an important role in erythropoiesis. In addition to its nuclear presence, Eklf was recently found to localise to the cytoplasm and this observation prompted us to examine whether this protein has a role as an RNA-binding protein, in addition to its well-characterised DNA-binding function. In this thesis we demonstrate that Eklf displays RNA-binding activity in an in vitro and in vivo context through the use of its classical zinc finger (ZF) domains. Furthermore, using two independent in vitro assays, we show that Eklf has a preference for A and U RNA homoribopolymers. These results represent the first description of RNA-binding by a member of the Klf family. We developed a dominant negative mutant of Eklf by expressing its ZF region in murine erythroleukaemia (MEL) cells. We used this to investigate the importance of this protein in haematopoietic lineage decisions by examining its effect on the multipotent K562 cell line. We provide evidence that Eklf appears to be critical not only for the promotion of erythropoiesis, but also for the inhibition of megakaryopoiesis.

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50

Hallal, Samantha. "Characterisation of the zinc fingers of Erythroid Kruppel-Like Factor". University of Sydney, 2008. http://hdl.handle.net/2123/4030.

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Doctor of Philosophy (PhD)
Gene expression is known to be regulated at the level of transcription. Recently, however, there has been a growing realisation of the importance of gene regulation at the post-transcriptional level, namely at the level of pre-mRNA processing (5’ capping, splicing and polyadenylation), nuclear export, mRNA localisation and translation. Erythroid krüppel-like factor (Eklf) is the founding member of the Krüppel-like factor (Klf) family of transcription factors and plays an important role in erythropoiesis. In addition to its nuclear presence, Eklf was recently found to localise to the cytoplasm and this observation prompted us to examine whether this protein has a role as an RNA-binding protein, in addition to its well-characterised DNA-binding function. In this thesis we demonstrate that Eklf displays RNA-binding activity in an in vitro and in vivo context through the use of its classical zinc finger (ZF) domains. Furthermore, using two independent in vitro assays, we show that Eklf has a preference for A and U RNA homoribopolymers. These results represent the first description of RNA-binding by a member of the Klf family. We developed a dominant negative mutant of Eklf by expressing its ZF region in murine erythroleukaemia (MEL) cells. We used this to investigate the importance of this protein in haematopoietic lineage decisions by examining its effect on the multipotent K562 cell line. We provide evidence that Eklf appears to be critical not only for the promotion of erythropoiesis, but also for the inhibition of megakaryopoiesis.

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