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National Repository of Grey Literature 2 records found  Search took 0.01 seconds. 
A role of the 5' cap in Sm-class snRNA biogenesis
 Petržílková, Hana ; Staněk, David (advisor) ; Abrhámová, Kateřina (referee)
Small nuclear RNAs (snRNAs) are the core component of the spliceosome which catalyzes pre-mRNA splicing. They undergo a complex biogenesis process which includes snRNA modifications and their assembly into ribonucleoprotein splicing particles snRNPs. The snRNA biogenesis pathway also includes several quality control steps, which block defective snRNPs from entering the spliceosome. One of the important feature involved in Sm-class snRNA quality control is the 5' trimethylguanosine cap (TMG). The capping of Sm-class snRNAs is also connected to the modifications of the first transcribed nucleotide, adenosine, which gets co-transcriptionally 2'-O-methylated and N6-methylated. However, the N6-methylation is later removed by FTO demethylase. Here I shed more light on functional relevance of the various modifications of snRNA 5' cap. I show that the N6-demethylation of the cap is important for normal metabolism of snRNAs, especially U2 snRNA. Next, I provide evidence that the 5' cap plays a role in quality control of 5' truncated snRNAs. Our data suggest that the truncated snRNAs accumulate immature monomethylated caps and are bound by a specific cap binding complex IFIT1/2/3. I propose that the 5' truncated snRNAs are partially stalled in early stages of snRNA biogenesis and are targeted by quality...
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The role of the m6A pathway on electrophysiological correlates of spatial memory in animal model of Alzheimer's disease
 Karkušová, Patrícia ; Telenský, Petr (advisor) ; Hromádka, Tomáš (referee)
Memory is one of the vital cognitive functions and can be divided into two categories, short-term memory and long-term memory. Long - term memory is further divided into explicit (declarative) for facts and events and implicit (non-declarative) memory, covering all other types of long-term memory. Alzheimer's disease is well known for a gradual loss of declarative memory and spatial orientation. It is one of the most common causes of dementia and affects tens of millions of people worldwide. The aim of our study was to determine the effect of inhibition of FTO demethylase on neuronal activity in a rat model of Alzheimer's disease (TgF344-AD) and a control strain (F344-CT), and evaluate the stability of spatial maps. We used tetrodes implanted in hippocampal CA1 subregion to record extracellular neuronal activity. Spiking activity was recorded in two spatially different conditions (familiar, unknown) twice, before and after applications of pharmacological inhibitor of FTO demethylase (MO-I-500). We have also evaluated remapping and map stability related to the application of MO-I- 500. We found the average frequency of neuronal firing rate increased in F344-CT rats in both familiar and novel environments after inhibitor administration, whereas increase in TgF344- AD rats was detected only in the novel...
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