On 11 September at 13:15 Baiba Brumele will defend her doctoral thesis “Uncovering the TRMT112 methyltransferase network and characterising the cellular functions of TRMT112-network member N6AMT1” for obtaining the degree of Doctor of Philosophy (Biomedical Engineering)
Supervisors:
Professor Reet Kurg, University of Tartu
Research Fellow Margit Mutso, University of Tartu
Opponent:
Marc Graille, CNRS Research Director (1st class), Laboratory of Biochemistry, France
Summary:
The aim of this doctoral thesis was to investigate the evolutionarily conserved methyltransferase-activator TRMT112 and its interacting methyltransferases with a particular focus on the interaction partner N6AMT1.
Methyltransferases are a specific group of proteins that add a methyl group to different substrates such as RNA, DNA, and other proteins, and by doing so alter the behaviour of the substrate inside the cells. Studies have shown that dysfunction of various methyltransferases can lead to numerous diseases, ranging from neurodegenerative disorders to cancer. Therefore, it is necessary to fully understand the complex functions and interaction networks of these proteins in human cells. In eukaryotic cells, the methyltransferase cofactor TRMT112 and methyltransferases that bind to TRMT112 are important regulators of protein synthesis. Nonetheless, knowledge about TRMT112-network methyltransferases and their functions in human cells is still limited.
The results of this thesis revealed that TRMT112 interacts with at least seven methyltransferases: N6AMT1, WBSCR22, METTL5, ALKBH8, TRMT11, THUMPD2 and THUMPD3 in human cells. In addition TRMT112 and its interacting methyltransferases showed a mutual stabilisation effect on each other in human cells. It was also shown that the TRMT112-network methyltransferase N6AMT1 is involved in the regulation of cell proliferation, as its depletion led to an increase in cell doubling time and impaired cell cycle progression, in particular progression out of mitosis and G1/S transition. Additionally, N6AMT1 depleted cells showed a decreased level of cyclin E, an essential regulator of the G1/S transition, at both protein and mRNA levels. Lastly, it was shown that several commercially available antibodies targeting N6AMT1 cross-react with the mitosis-associated protein Aurora kinase A, likely due to the presence of a shared, unique ENNPEE motif found only in these two proteins. Altogether, the findings of this thesis expand our understanding of the TRMT112 methyltransferase network and contribute to a better understanding of methyltransferase-associated cellular processes in human cells.
Defence can be followed in Zoom: Doctoral Defence (meeting ID: 953 058 8152, passcode: kaitsmine).
