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The role of pre-mRNA splicing in human hereditary diseases
Malinová, Anna ; Staněk, David (advisor) ; Vanáčová, Štěpánka (referee) ; Krásný, Libor (referee)
U5 small ribonucleoprotein particle (U5 snRNP) is a crucial component of the spliceosome, the complex responsible for pre-mRNA splicing. Despite the importance of U5 snRNP, not much is known about its biogenesis. When we depleted one of the core U5 components, protein PRPF8, the other U5-specific proteins do not associate with U5 snRNA and the incomplete U5 was accumulated in nuclear structures known as Cajal bodies. To further clarify the role of PRPF8 in U5 snRNP assembly, we studied PRPF8 mutations that cause an autosomal dominant retinal disorder, retinitis pigmentosa (RP). We prepared eight different PRPF8 variants carrying RP-associated mutations and expressed them stably in human cell culture. We showed that most mutations interfere with the assembly of snRNPs which consequently leads to reduced efficiency of splicing. The mutant PRPF8 together with EFTUD2 are stalled in the cytoplasm in a form of U5 snRNP assembly intermediate. Strikingly, we identified several chaperons including the HSP90/R2TP complex and ZNHIT2 as new PRPF8's interactors and potential U5 snRNP assembly factors. Our results further imply that these chaperons preferentially bind the unassembled U5 complexes and that HSP90 is required for stability of...
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Renaissance sgraffito decoration of castles Benátky nad Jizerou, Nelahozeves and Brandýs nad Labem
Malinová, Anna ; Jarošová, Markéta (advisor) ; Nespěšná Hamsíková, Magdaléna (referee)
Bibliographic Citation Renaissance sgraffito decoration of castles Benátky nad Jizerou, Nelahozeves and Brandýs nad Labem: bachelor thesis / Anna Malinová; supervisor: PhDr. Markéta Jarošová, PhD. -- Prague, 2021. -- 98 p. Abstract In this bachelor thesis, I focus on the exterior mural sgraffito décor of three Renaissance castles connected by the Royal Bohemian smelter. I concentrate this thesis on the cultural and historical context of the Renaissance Art period in the area of the Bohemian kingdom, the sgraffito craftsmanship, and its development in the Northern European regions. For this work, I have chosen three renaissance castles - Benátky nad Jizerou, Nelahozeves and Brandýs nad Labem. Firstly I will introduce their historical value and I will explain connections between the castles, the Royal Bohemian smelter, and the Renaissance sgraffito decoration, which I will also use to analyze singular iconographical motives, to which I will add the original graphical artworks, that were used as examples for illustrating particular scenes and topics. As a conclusion, I will try to compare the artistic level of mural sgraffito decorations and I will also add some more examples of this kind of decoration in the same period, location, and quality. Keywords Renaissance Art, sgraffito, renaissance mural paintings...
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The role of pre-mRNA splicing in human hereditary diseases
Malinová, Anna
U5 small ribonucleoprotein particle (U5 snRNP) is a crucial component of the spliceosome, the complex responsible for pre-mRNA splicing. Despite the importance of U5 snRNP, not much is known about its biogenesis. When we depleted one of the core U5 components, protein PRPF8, the other U5-specific proteins do not associate with U5 snRNA and the incomplete U5 was accumulated in nuclear structures known as Cajal bodies. To further clarify the role of PRPF8 in U5 snRNP assembly, we studied PRPF8 mutations that cause an autosomal dominant retinal disorder, retinitis pigmentosa (RP). We prepared eight different PRPF8 variants carrying RP-associated mutations and expressed them stably in human cell culture. We showed that most mutations interfere with the assembly of snRNPs which consequently leads to reduced efficiency of splicing. The mutant PRPF8 together with EFTUD2 are stalled in the cytoplasm in a form of U5 snRNP assembly intermediate. Strikingly, we identified several chaperons including the HSP90/R2TP complex and ZNHIT2 as new PRPF8's interactors and potential U5 snRNP assembly factors. Our results further imply that these chaperons preferentially bind the unassembled U5 complexes and that HSP90 is required for stability of...
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The role of pre-mRNA splicing in human hereditary diseases
Malinová, Anna
U5 small ribonucleoprotein particle (U5 snRNP) is a crucial component of the spliceosome, the complex responsible for pre-mRNA splicing. Despite the importance of U5 snRNP, not much is known about its biogenesis. When we depleted one of the core U5 components, protein PRPF8, the other U5-specific proteins do not associate with U5 snRNA and the incomplete U5 was accumulated in nuclear structures known as Cajal bodies. To further clarify the role of PRPF8 in U5 snRNP assembly, we studied PRPF8 mutations that cause an autosomal dominant retinal disorder, retinitis pigmentosa (RP). We prepared eight different PRPF8 variants carrying RP-associated mutations and expressed them stably in human cell culture. We showed that most mutations interfere with the assembly of snRNPs which consequently leads to reduced efficiency of splicing. The mutant PRPF8 together with EFTUD2 are stalled in the cytoplasm in a form of U5 snRNP assembly intermediate. Strikingly, we identified several chaperons including the HSP90/R2TP complex and ZNHIT2 as new PRPF8's interactors and potential U5 snRNP assembly factors. Our results further imply that these chaperons preferentially bind the unassembled U5 complexes and that HSP90 is required for stability of...
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The role of pre-mRNA splicing in human hereditary diseases
Malinová, Anna ; Staněk, David (advisor) ; Vanáčová, Štěpánka (referee) ; Krásný, Libor (referee)
U5 small ribonucleoprotein particle (U5 snRNP) is a crucial component of the spliceosome, the complex responsible for pre-mRNA splicing. Despite the importance of U5 snRNP, not much is known about its biogenesis. When we depleted one of the core U5 components, protein PRPF8, the other U5-specific proteins do not associate with U5 snRNA and the incomplete U5 was accumulated in nuclear structures known as Cajal bodies. To further clarify the role of PRPF8 in U5 snRNP assembly, we studied PRPF8 mutations that cause an autosomal dominant retinal disorder, retinitis pigmentosa (RP). We prepared eight different PRPF8 variants carrying RP-associated mutations and expressed them stably in human cell culture. We showed that most mutations interfere with the assembly of snRNPs which consequently leads to reduced efficiency of splicing. The mutant PRPF8 together with EFTUD2 are stalled in the cytoplasm in a form of U5 snRNP assembly intermediate. Strikingly, we identified several chaperons including the HSP90/R2TP complex and ZNHIT2 as new PRPF8's interactors and potential U5 snRNP assembly factors. Our results further imply that these chaperons preferentially bind the unassembled U5 complexes and that HSP90 is required for stability of...
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Incidence and molecular typing of Clostridium difficile strains in the Czech republic
Malinová, Anna ; Jirásková, Alena (advisor) ; Čáp, Michal (referee)
Clostridium difficile is a major cause of infectious diarrhea in hospitalized patients. Clostridium difficile-associated disease (CDAD) is of gaining importance now due to its increasing incidence and severity. However, little is known about the C. difficile infections in the Czech Republic. The aim of the study was to characterize C. difficile strains recently isolated (2008 to 2011) from patients hospitalized with gastrointestinal disease in four Prague health care institutions using molecular typing methods; PCR toxinotyping, PCR ribotyping and MLVA (multilocus variable number tandem repeat analysis). Among 273 C. difficile strains, we identified 8 toxinotypes (0, III, IV, V, VI, VIII, IX a XXIII) and 63 ribotypes, of which ribotypes 596 (23,4 % patient), 017 (13,9 %) and 176 (7 %) were the most frequent. According to PCR ribotyping, the situation in the Czech Republic is the most similar to the situation in Poland. Within ribotypes 017, 017/1 and 017/2 and ribotypes 596 and 596/1, 5 and 4 distinct clusters were identified by MLVA, none of which was institution-specific. Additionally, pathogenic C.difficile were isolated from piglet faeces (63,3 %) in a single piglet farm, evaluating the role of C. difficile as an emerging animal pathogen. All piglet isolates belonged to the toxinotype 0 and the ribotype...
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