Alternative titles; symbols
HGNC Approved Gene Symbol: TRMT112
Cytogenetic location: 11q13.1 Genomic coordinates (GRCh38): 11:64,316,460-64,318,596 (from NCBI)
TRM112 is an evolutionarily conserved methyltransferase-interacting protein (van Tran et al., 2018).
Gross (2019) mapped the TRMT112 gene to chromosome 11q13.1 based on an alignment of the TRMT112 sequence (GenBank BC017172) with the genomic sequence (GRCh38).
Sardana and Johnson (2012) showed that yeast Bud23 (615733) and Trm112 physically and functionally interacted and that their mutants were defective for the same step in 40S ribosomal subunit biogenesis. Trm112 was required for both 40S and 60S biogenesis, but it predominantly sedimented with 60S in a Bud23-independent manner. Trm112 specifically interacted with the 60S-related methyltransferases Nop2 (164031) and Rcm1 (NSUN5; 615732). Interaction with Trm112 affected the stability of some, but not all, of its partners.
Van Tran et al. (2018) functionally and structurally characterized the Trm112 protein network in Haloferax volcanii and identified 8 different methyltransferases that interacted directly with Trm112. Functional and structural analyses suggested that these methyltransferases share similar methyltransferase functions as their eukaryotic orthologs.
Van Tran et al. (2019) identified METTL5 (618628) as the human methyltransferase responsible for N6 methylation of A1832 (m6A1832) on 18S rRNA. METTL5 interacted directly with TRMT112, forming a heterodimer that provided metabolic stability for METTL5.
Van Tran et al. (2019) obtained the crystal structure of the human METTL5-TRMT112 complex at 1.6-angstrom resolution. TRMT112 contained a zinc-binding domain (ZBD) and a central domain. The ZBD consisted of an alpha helix packed against a 4-stranded antiparallel beta sheet. The ZBD of human TRMT112 lacked the 4 cysteines conserved among other eukaryotic Trm112 proteins and therefore did not bind zinc. The central domain consisted of 3 alpha helices. METTL5 consisted of a single domain adopting a class I S-adenosylmethionine (SAM)-dependent methyltransferase fold composed of a central 7-stranded beta sheet flanked by 4 alpha helices on one side and 2 on the other. The METTL5-TRMT112 interface was formed by 29 METTL5 residues and 28 TRMT112 residues and was characterized by a large central hydrophobic core. The hydrophobic interface was surrounded by polar residues involved in formation of 8 hydrogen bonds and 2 salt bridges. A large hydrophobic surface on METTL5 was masked by TRMT112 upon complex formation, providing stability to METTL5 in solution.
Gross, M. B. Personal Communication. Baltimore, Md. 10/16/2019.
Sardana, R., Johnson, A. W. The methyltransferase adaptor protein Trm112 is involved in biogenesis of both ribosomal subunits. Molec. Biol. Cell 23: 4313-4322, 2012. [PubMed: 22956767] [Full Text: https://doi.org/10.1091/mbc.E12-05-0370]
van Tran, N., Ernst, F. G. M., Hawley, B. R., Zorbas, C., Ulryck, N., Hackert, P., Bohnsack, K. E., Bohnsack, M. T., Jaffrey, S. R., Graille, M., Lafontaine, D. L. J. The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. Nucleic Acids Res. 47: 7719-7733, 2019. [PubMed: 31328227] [Full Text: https://doi.org/10.1093/nar/gkz619]
van Tran, N., Muller, L., Ross, R. L., Lestini, R., Letoquart, J., Ulryck, N., Limbach, P. A., de Crecy-Lagard, V., Cianferani, S., Graille, M. Evolutionary insights into Trm112-methyltransferase holoenzymes involved in translation between archaea and eukaryotes. Nucleic Acids Res. 46: 8483-8499, 2018. [PubMed: 30010922] [Full Text: https://doi.org/10.1093/nar/gky638]