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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 function of 2'-O-methylated RNA in the context of viral infection
Potužník, Jiří ; Macíčková Cahová, Hana (advisor) ; Forstová, Jitka (referee)
RNA is subject to a wide array of post-transcriptional modifications. 2'-O-methylation is an essential intrinsic modification of RNA. It affects the structure and reactivity of the molecule as well as its function. 2'-O-methylation is highly conserved, present in all three domains of life. Viral RNA uses this modification to mimic the host and evade detection by the immune system. There are two main mechanisms, through which viral 2'-O-methylated RNA does this. The first is evading detection by a pattern recognition receptor form the RIG-I-like receptor family Mda5. Mda5 is capable of detecting unmethylated RNA and recognising it as non-self, thus initiating an immune response. The second mechanism the evasion and restriction of an effector molecule IFIT. IFIT proteins are capable of detecting the absence of 2'-O- methylation on viral RNAs and inhibiting their translation. They do this by interfering with the formation of the ternary complex, an essential member of ribosomal formation. Using viral 2'- O-methylation as a target for therapy, it is possible to develop attenuated vaccines. Keywords: viral RNA, RNA modifications, 2'-O-methylation, Mda5, IFIT, RIG-I-like receptors, epitranscriptomics, WNV, JEV
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