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The role of a specific miRNAs in the regulation of apoptosis during physiological and pathophysiological processes in the CNS
Kaslová, Tereza ; Romanyuk, Natalyia (advisor) ; Klassen, Ruslan (referee)
MicroRNAs are small non-coding RNAs of 20 to 24 nucleotides in size that are able to post- transcriptionally regulate gene expression by binding to mRNA. This paper focuses on how these microRNAs are generated and how they are able to regulate at the level of proteins involved in programmed cell death - apoptosis. By what mechanisms apoptosis occurs, what proteins are involved and what changes the cell undergoes are further discussed in this thesis. The precise influence of this post-transcriptional regulation is presented by using selected microRNAs that influence apoptosis during the development of the central nervous system, as well as during and as a consequence of the neurodegenerative diseases and damage that can affect it. Finally, it will also introduce the use of microRNAs as potential biomarkers, due to changes in their levels associated with various diseases, and as direct therapeutic targets. Keywords Apoptosis, microRNA, cell death, central nervous system, neurodegenerative diseases, gene expression regulation
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tsRNA - biogenesis, regulation and function in gene expression
Ramanava, Marharyta ; Mašek, Tomáš (advisor) ; Fryaufová, Petra (referee)
Transfer RNA (tRNA) accounts for approximately 10% of total cellular RNA pool and plays a crucial role in translation. Here I focus on the alternative function of tRNA, which can serve as a precursor for the formation of so-called "small RNAs derived from tRNA" (tsRNAs). These small non-coding RNAs are primarily generated by the cleavage of tRNAs by the ribonucleases Angiogenin and Dicer. tRFs (tRNA-derived fragments) and tiRNAs (stress- induced RNA-derived RNAs) are two major classes that differ fundamentally in the position of the cleavage site in the parent tRNA and the length of the molecule. Some tsRNAs act as regulators of posttranscriptional gene expression, often affecting mRNA stability and translation initiation. tsRNAs are implicated in regulation of stress response, cell differentiation, development, and apoptosis. Further, there is strong evidence that they have a role in epigenetic processes, communication between organs or even between organisms. In addition, in humans, their profile is often cell-specific and its change in pathophysiological conditions makes tsRNAs a suitable diagnostic marker. This work summarizes current knowledge about tsRNAs and their biological function and significance. Kaywords: small RNAs derived from tRNA; tRNA; tiRNA; tRF; gene expression regulation
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Transcription factors CSL and their role in the yeast Schizosaccharomyces pombe
Oravcová, Martina ; Převorovský, Martin (advisor) ; Heidingsfeld, Olga (referee) ; Krásný, Libor (referee)
Proteins of the CSL family (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) act as effectors of the Notch signalling pathway in metazoan organisms. They function as repressors or activators of gene transcription in the framework of this pathway and influence many developmental processes. Metazoan CSL proteins can regulate gene expression Notch-independently as well. Notch-independent functions of CSL proteins might be evolutionarily ancestral and in cells and organisms may be important equally as Notch-dependent functions. Presence of CSL proteins was identified in several fungal species, organisms lacking the Notch signalling pathway components and most of known metazoan interacting partners of CSL proteins. CSL paralogs of the fission yeast Schizosaccharomyces pombe, cbf11 and cbf12, are non-essential genes encoding proteins localized in the nucleus of the cell. They exert antagonistic effects on regulation of processes like coordination of nuclear and cellular division and cell cycle progression, ploidy maintenance, cell adhesion and other. In this study, we have proved that both CSL paralogs are able to sequence-specifically bind the CSL-response element DNA in vitro and Cbf11 in vivo as well. Both proteins could activate gene expression in vivo and perform the function of transcription factors....
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Gene expression regulation by nuclear receptors in a specific metabolic context - evolutionary perspective
Kaššák, Filip ; Kostrouch, Zdeněk (advisor) ; Macůrková, Marie (referee) ; Leontovyč, Ivan (referee)
In animals, some of the most critical regulators of gene expression are nuclear hormone receptors (NRs) and their coregulators, specifically the Mediator complex. Of particular interest are the NRs implicated in metabolic and developmental regulation and in carcinogenesis: thyroid hormone receptors (TRs) and retinoid X receptors (RXRs). In this work, I venture to elucidate some aspects of gene expression regulation by these NRs: the degree of evolutionary conservation of signalling based on NRs and their coregulators; the mechanisms of negative regulation by NRs; and possible implications of these findings for clinical medicine. State-of-the-art bioinformatical, genome editing and microscopic techniques are applied at three levels of animal evolution to study NRs and Mediator. Reverse genomics in human patients suffering from the syndrome of resistance to thyroid hormones β are used to infer the structure and function of TRβ subdomains. Alignments, binding studies and in vivo experiments in Trichoplax adhaerens allow identification of a close orthologue of human RXR at the basis of metazoan evolution. Employing database queries, genome editing and microscopy, we describe a correct orthologue of the Mediator subunit 28 in Caenorhabditis elegans, indicating a complete homology of the Mediator complex...
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Transcription factors CSL and their role in the yeast Schizosaccharomyces pombe
Oravcová, Martina
Proteins of the CSL family (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) act as effectors of the Notch signalling pathway in metazoan organisms. They function as repressors or activators of gene transcription in the framework of this pathway and influence many developmental processes. Metazoan CSL proteins can regulate gene expression Notch-independently as well. Notch-independent functions of CSL proteins might be evolutionarily ancestral and in cells and organisms may be important equally as Notch-dependent functions. Presence of CSL proteins was identified in several fungal species, organisms lacking the Notch signalling pathway components and most of known metazoan interacting partners of CSL proteins. CSL paralogs of the fission yeast Schizosaccharomyces pombe, cbf11 and cbf12, are non-essential genes encoding proteins localized in the nucleus of the cell. They exert antagonistic effects on regulation of processes like coordination of nuclear and cellular division and cell cycle progression, ploidy maintenance, cell adhesion and other. In this study, we have proved that both CSL paralogs are able to sequence-specifically bind the CSL-response element DNA in vitro and Cbf11 in vivo as well. Both proteins could activate gene expression in vivo and perform the function of transcription factors....
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Role of long non-coding RNAs in plants
Klodová, Božena ; Honys, David (advisor) ; Novotný, Marian (referee)
Long non-coding RNAs (lncRNAs) represent a group of transcripts with length greater than 200 nucleotides having low coding potential. It is a group of regulatory ribonucleic acid (RNA) still not fully understood but with significant potential in many biological processes across different species. For animals, many important lncRNA regulators and their roles in a range of events including their involvement in carcinogenic diseases have been reported. However, particular mechanisms of functions are often yet to be discovered. Considering plants, economically important species such as rice, maize or soybean are of particular interest. There are still only several fully annotated transcripts. However, with the constant improvement of sequencing and bioinformatic methods, the importance of lncRNA (for example in pathogen resistance or plant reproduction) becomes clear. This bachelor thesis reviews up-to-date knowledge about lncRNAs and their roles in plants. It also describes the difficulties of lncRNA research and discusses their future potential.
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Transcription factors CSL and their role in the yeast Schizosaccharomyces pombe
Oravcová, Martina ; Převorovský, Martin (advisor) ; Heidingsfeld, Olga (referee) ; Krásný, Libor (referee)
Proteins of the CSL family (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) act as effectors of the Notch signalling pathway in metazoan organisms. They function as repressors or activators of gene transcription in the framework of this pathway and influence many developmental processes. Metazoan CSL proteins can regulate gene expression Notch-independently as well. Notch-independent functions of CSL proteins might be evolutionarily ancestral and in cells and organisms may be important equally as Notch-dependent functions. Presence of CSL proteins was identified in several fungal species, organisms lacking the Notch signalling pathway components and most of known metazoan interacting partners of CSL proteins. CSL paralogs of the fission yeast Schizosaccharomyces pombe, cbf11 and cbf12, are non-essential genes encoding proteins localized in the nucleus of the cell. They exert antagonistic effects on regulation of processes like coordination of nuclear and cellular division and cell cycle progression, ploidy maintenance, cell adhesion and other. In this study, we have proved that both CSL paralogs are able to sequence-specifically bind the CSL-response element DNA in vitro and Cbf11 in vivo as well. Both proteins could activate gene expression in vivo and perform the function of transcription factors....
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Pleiotropic effects of transcriptional protein Opi1 in Saccharomyces cerevisiae
Pavlíčková, Martina ; Schierová, Michaela (advisor) ; Mašek, Tomáš (referee)
Phospholipid biosynthesis in Sacchromyces cerevisiae is regulated by Ino2p-Ino4p activation complex and Opi1p repressor. The most highly regulated INO1 gene encodes inositol-3- phosphate synthase. This enzyme catalyzes the first step of the metabolic pathway of inositol synthesis. The Ino2p-Ino4p activation complex binds to the promoter of the target genes and interacts with other proteins necessary for activation (Snf1p, SAGA, SWI/SNF, INO80). The Opi1p represses transcription by direct binding to Ino2p and by interaction with other proteins (Sin3p, Cyc8p). The activity of Opi1p protein is mediated by cellular localization and by phosphorylation. The regulation of phospholipids is dependent on the growth phase and on the availability of precursors. Apart from its repressor activity, Opi1p affects mitochondrial metabolism, endoplasmic reticulum stress, cell size, mat formation and invasive growth.
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Transcription factors CSL and their role in the yeast Schizosaccharomyces pombe
Oravcová, Martina
Proteins of the CSL family (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) act as effectors of the Notch signalling pathway in metazoan organisms. They function as repressors or activators of gene transcription in the framework of this pathway and influence many developmental processes. Metazoan CSL proteins can regulate gene expression Notch-independently as well. Notch-independent functions of CSL proteins might be evolutionarily ancestral and in cells and organisms may be important equally as Notch-dependent functions. Presence of CSL proteins was identified in several fungal species, organisms lacking the Notch signalling pathway components and most of known metazoan interacting partners of CSL proteins. CSL paralogs of the fission yeast Schizosaccharomyces pombe, cbf11 and cbf12, are non-essential genes encoding proteins localized in the nucleus of the cell. They exert antagonistic effects on regulation of processes like coordination of nuclear and cellular division and cell cycle progression, ploidy maintenance, cell adhesion and other. In this study, we have proved that both CSL paralogs are able to sequence-specifically bind the CSL-response element DNA in vitro and Cbf11 in vivo as well. Both proteins could activate gene expression in vivo and perform the function of transcription factors....
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