| Structural highlights
6h2v is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.49Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TR112_HUMAN Acts as an activator of both rRNA/tRNA and protein methyltransferases (PubMed:25851604). Together with methyltransferase BUD23, methylates the N(7) position of a guanine in 18S rRNA (PubMed:25851604). The heterodimer with HEMK2/N6AMT1 catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:18539146). The heterodimer with ALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA species (PubMed:20308323). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production (PubMed:25851604).[1] [2] [3]
Publication Abstract from PubMed
N6-methyladenosine (m6A) has recently been found abundantly on messenger RNA and shown to regulate most steps of mRNA metabolism. Several important m6A methyltransferases have been described functionally and structurally, but the enzymes responsible for installing one m6A residue on each subunit of human ribosomes at functionally important sites have eluded identification for over 30 years. Here, we identify METTL5 as the enzyme responsible for 18S rRNA m6A modification and confirm ZCCHC4 as the 28S rRNA modification enzyme. We show that METTL5 must form a heterodimeric complex with TRMT112, a known methyltransferase activator, to gain metabolic stability in cells. We provide the first atomic resolution structure of METTL5-TRMT112, supporting that its RNA-binding mode differs distinctly from that of other m6A RNA methyltransferases. On the basis of similarities with a DNA methyltransferase, we propose that METTL5-TRMT112 acts by extruding the adenosine to be modified from a double-stranded nucleic acid.
The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112.,van Tran N, Ernst FGM, Hawley BR, Zorbas C, Ulryck N, Hackert P, Bohnsack KE, Bohnsack MT, Jaffrey SR, Graille M, Lafontaine DLJ Nucleic Acids Res. 2019 Jul 22. pii: 5536363. doi: 10.1093/nar/gkz619. PMID:31328227[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Figaro S, Scrima N, Buckingham RH, Heurgue-Hamard V. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett. 2008 Jul 9;582(16):2352-6. doi: 10.1016/j.febslet.2008.05.045. Epub, 2008 Jun 6. PMID:18539146 doi:http://dx.doi.org/10.1016/j.febslet.2008.05.045
- ↑ Fu D, Brophy JA, Chan CT, Atmore KA, Begley U, Paules RS, Dedon PC, Begley TJ, Samson LD. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol Cell Biol. 2010 May;30(10):2449-59. doi: 10.1128/MCB.01604-09. Epub 2010 Mar , 22. PMID:20308323 doi:http://dx.doi.org/10.1128/MCB.01604-09
- ↑ Zorbas C, Nicolas E, Wacheul L, Huvelle E, Heurgue-Hamard V, Lafontaine DL. The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis. Mol Biol Cell. 2015 Jun 1;26(11):2080-95. doi: 10.1091/mbc.E15-02-0073. Epub 2015, Apr 7. PMID:25851604 doi:http://dx.doi.org/10.1091/mbc.E15-02-0073
- ↑ van Tran N, Ernst FGM, Hawley BR, Zorbas C, Ulryck N, Hackert P, Bohnsack KE, Bohnsack MT, Jaffrey SR, Graille M, Lafontaine DLJ. The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. Nucleic Acids Res. 2019 Jul 22. pii: 5536363. doi: 10.1093/nar/gkz619. PMID:31328227 doi:http://dx.doi.org/10.1093/nar/gkz619
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