Characterization of the TRMT112-methyltransferase network in mammalian cells

Abstract

TRMT112 is a small evolutionary conserved protein that acts as a co-factor and activator for different methyltransferases involved in rRNA, tRNA and protein methylation. In mammalian cells TRMT112 interacts with WBSCR22, N6AMT1, METTL5, ALKBH8, TRMT11, THUMPD2 and THUMPD3. During this research subcellular localisation and mutual interactions of TRMT112 and its partners were studied. TRMT112 level and localization in the cells is tightly regulated and there is a positive feedback loop between TRMT112 and its partners. TRMT112 interacts with all its partners in a similar way, but single amino acid mutations on the surface of TRMT112 reveal several differences as well. Lastly, partial genomic knockout of TRMT112 using CRISPR/Cas9 system significantly reduces WBSCR22 protein level in mammalian cells. In summary, mammalian TRMT112 can be considered as a central “hub” protein that regulates the activity of several of the methyltransferases it interacts with.