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The role of the m6A pathway in the regulation of brain ontogenesis in the rat
Tabáková, Petra ; Telenský, Petr (advisor) ; Holzerová, Kristýna (referee)
N6-methyladenosine (m6A) is the most ubiquitous post-transcriptional RNA modification and has an important role in determining the fate of mRNA transcripts. Among the key proteins of the m6A pathway are methyltransferases (METTL family enzymes), demethylases (FTO, ALKBH family enzymes), and m6A binding proteins (e.g., YTHDF family) which recognize RNA sequences depending on the amount and localization of m6A in target transcripts and subsequently influence the fate of mRNA transcripts. The role of methyltransferases and demethylases is to provide a dynamic balance of m6A levels and possibly to convey mechanisms of specificity for these so-called epitranscriptomic marks, which are not yet fully understood. The main objective of this work was to determine the relative changes in the expression of key m6A pathway proteins during early postnatal development and adulthood in the rat brain. We found that the level of expression of key m6A pathway proteins decreases from birth to adulthood, with the exception of a transient increase between postnatal days 10 and 18. During this period, we also found significant changes in the expression of respiratory chain complexes. However, further research is needed to provide evidence of a mechanistic link between the m6A pathway and brain energy homeostasis during...
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m6A RNA methylation in eukaryotic cells
Petržílková, Hana ; Staněk, David (advisor) ; Folk, Petr (referee)
The N6-methylation of adenosine (m6 A) is the most abundant modification in eukaryotic mRNA. This modification is deposited on RNA co-transcriptionally by the methyltransferase complexes and can also be "erased" by specific demethylases. The existence of m6 A demethylases makes the modification reversible and potentially dynamic, therefore, m6 A could have a function in gene expression regulation. Since the discovery of the first m6 A demethylase FTO, the m6 A has become a hot-topic in RNA-biology research. m6 A is found in mRNAs but also in various non-coding RNAs. Analysis of m6 A distribution on mRNAs revealed the enrichment of m6 A in proximity of a stop codon, in 3' UTRs and possibly around 5' and 3' splice-sites. So far two m6 A methyltransferases have been discovered in vertebrates, METTL3/METTL14 complex is the major methyltransferase and METTL16 deposits m6 A just on a specific subset of RNAs. Additionally, two m6 A demethylases are known - FTO and ALKBH5. Finally, members of protein family with a so-called YTH RNA binding domain were identified as m6 A binding proteins. m6 A serves as a signal affecting various steps of RNA metabolism such as mRNA splicing, nuclear export, translation or RNA degradation. Some of the effects are clearly mediated by the m6 A binding proteins, but also other...
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