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The role of SNW/SKIP proteins in splicing
Hollá, Sandra ; Novotný, Marian (advisor) ; Kozáková, Eva (referee)
SNW proteins are essential nuclear factors whose name was derived from the conserved motif SNW. They can be found with various representatives across the eukaryotic empire. SNW proteins are involved in regulating many cellular processes - for example regulation of gene expression and cell cycle. By far the most information about the function of human homologue provides SKIP/NCoA-62, which was found in a number of signaling pathways. Yet it is not fully understood the function of SNW proteins. In this work, I would like to focus on the role of SNW proteins in pre-mRNA splicing, particularly in the yeast Saccharomyces cerevisiae, where most results were acquired. Key words: SNW protein, Prp45, splicing pre-mRNA, SKIP/NCoA-62, Prp22
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Self-attribution in Schizophrenia
Kozáková, Eva ; Kulišťák, Petr (advisor) ; Michalec, Jiří (referee) ; Drozdová, Kristýna (referee)
Background: Schizophrenia is a mental disorder with highly variable clinical presentation. It has been proposed that the unifying characteristic across all its variants is a disturbance of self/other boundaries and distinction. However, the understanding of its mechanism is still emerging. The presented thesis examines the hallmark feature of altered self-attribution of agency (SA) in schizophrenia with the aim to depict the underlying and related processes. Objectives: The experimental part consists of three separate studies. The first study verifies whether SA alterations reported in the literature are not confounded by an impairment of broader sensorimotor capacities. Further, it focuses on the association between SA alterations in schizophrenia and symptom severity and their dependence in time. The second study examines the differences in brain activity between patients and healthy controls during SA processing. The last study investigates the possible role of intrinsic brain connectivity in self-agency processing. Methods: The studies combine data from the levels of clinical presentation (symptoms), behavioral performance, and brain activity. More than 300 participants were involved in the studies in total. We used a behavioral SA task and a control task; the Positive and Negative Syndrome...
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Does the pre-mRNA splicing occur in S. cerevisiae co- or post-transcriptionally?
Cihlářová, Zuzana ; Půta, František (advisor) ; Kozáková, Eva (referee)
Until recently, the splicing and transcription were seen as almost independent processes. However, today a lot of studies provide plenty of evidence about their connection, even in the yeast Saccharomyces cerevisiae. The connection of these processes is particularly mediated by C-terminal domain of RNA polymerase II, which is consisted of tandemly repeated heptapeptide sequence - YSPTSPS. Amino acid residues of this heptapeptide sequence are specifically phosphorylated during transcription, which regulates transcription process and also the binding of specific factors. These factors are necessary for processing of the nascent transcript. Modifications of the primary transcript occur especially cotranscriptionally in higher eukaryotes, thus before the transcription is terminated and also before the functional mRNA is released. Opinion on cotranscriptional splicing in S. cerevisiae were significantly changed in the last years. However, nowadays the splicing of pre-mRNA of most genes in S. cerevisiae is seen as cotranscriptional process. RNA polymerase II pauses within the terminal exons and this pausing event provides sufficient time for each spliceosomal component to assemble on the pre-mRNA and also for catalysis of splicing before the transcription termination. Keywords: cotranscriptional...
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Role of promoter in the regulation of alternative splicing
Kozáková, Eva ; Staněk, David (advisor) ; Půta, František (referee) ; Blažek, Dalibor (referee)
It was shown that 95 % of human multi-exon genes are alternatively spliced and the regulation of alternative splicing is extremely complex. Most pre-mRNA splicing events occur co- transcriptionally and there is increasing body of evidence, that chromatin modifications play an important role in the regulation of alternative splicing. Here we showed that inhibition of histone deacetylases (HDACs) modulates alternative splicing of ~700 genes via induction of histone H4 acetylation and increase of Pol II elongation rate along alternative region. We identified HDAC1 the catalytic activity of which is responsible for changes in alternative splicing. Then, we analyzed whether acetylhistone binding protein Brd2 regulates alternative splicing and showed that Brd2 occupies promoter regions of targeted genes and controls alternative splicing of ~300 genes. Later we showed that knockdown of histone acetyltransferase p300 promotes inclusion of the alternative fibronectin (FN1) EDB exon. p300 associates with CRE sites in the promoter via the CREB transcription factor. We created mini-gene reporters driven by an artificial promoter containing CRE sites. Both deletion and mutation of the CRE site affected EDB alternative splicing in the same manner as the p300 knockdown. Next we showed that p300 controls histone...
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The Effectiveness of Cognitive Training in Patients after Traumatic Brain Injury or Stroke
Kozáková, Eva ; Kulišťák, Petr (advisor) ; Stehlík, Luděk (referee)
Recently, the literature concerned with the possibilities and limitations of working memory training has been growing rapidly. Nonetheless, there are still no clear answers about the principles of its effectiveness or transfer effect. The main questions we ask are about effectiveness of cognitive training in patients after stroke or TBI. To our knowledge this group hasn't been studied in this context yet. To do this, we compare two types of cognitive training - extensively studied N-back training (n=11) and still more popular group cognitive therapy (n=9) with a placebo control group (n=5) who recieves "training" in a simple computer game. The placebo control group then continues in N-back training. Our hypothesis is that after 3 weeks the two trainings should lead to significantly higher gains in cognitive tests scores than the placebo condition. Also, we expected N-back to be more effective than group cognitive training in domains more closely related to executive control. We tested attention, fluid intelligence, short-term and working memory. We also recorded participants well-being. Following training, there were no significant differences between N-back and group training. N-back group scored significantly higer on Trail Making Test A than control group (p=0,026). Although our study doesn't...
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The role of SNW/SKIP proteins in splicing
Hollá, Sandra ; Novotný, Marian (advisor) ; Kozáková, Eva (referee)
SNW proteins are essential nuclear factors whose name was derived from the conserved motif SNW. They can be found with various representatives across the eukaryotic empire. SNW proteins are involved in regulating many cellular processes - for example regulation of gene expression and cell cycle. By far the most information about the function of human homologue provides SKIP/NCoA-62, which was found in a number of signaling pathways. Yet it is not fully understood the function of SNW proteins. In this work, I would like to focus on the role of SNW proteins in pre-mRNA splicing, particularly in the yeast Saccharomyces cerevisiae, where most results were acquired. Key words: SNW protein, Prp45, splicing pre-mRNA, SKIP/NCoA-62, Prp22
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The role of tyrosine phosphorylation in hnRNA splicing
Koudelková, Lenka ; Brábek, Jan (advisor) ; Kozáková, Eva (referee)
Coding sequences of eukaryotic genes are interrupted by long segments of noncoding intronic DNA, which must be spliced after a transcription into a heterogenous nuclear RNA. Due to an increasing pressure on complexity of proteome eukaryotic organisms evolved alternative splicing. It is enabled through weak consensus sequences of splice sites flanked with accessory regulatory RNA elements, that associate with splicing factors, to create protein products according to current requirements implicated by outer and inner conditions. The net of cooperatively or antagonistic acting factors determines whether splice sites are recognized or not. This molecular system is regulated by enzymatic modifications depending on activity of corresponding signaling pathways. Beside many other enzymes a family of protein tyrosine kinases is involved in the process. Via catalytic activity of their kinase domains, they add phosphate to tyrosines of proteins that participate in RNA metabolism. Phosphorylation affects their affinity for RNA and other interacting partners, localization, enzymatic activity or other properties. The changes result in establishing of new setting of regulatory net and usage of distinct splice sites. Products then may with a different efficiency inhibit or trigger various cell processes or...
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