To date, about 90 post-transcriptional modifications have been reported in tRNA expanding their chemical and functional diversity. Methylation is the most frequent post-transcriptional tRNA modification that can occur on almost all nitrogen sites of the nucleobases, on the C5 atom of pyrimidines, on the C2 and C8 atoms of adenosine and, additionally, on the oxygen of the ribose 2′-OH. The methylation on the N1 atom of adenosine to form 1-methyladenosine (m1A) has been identified at nucleotide position 9, 14, 22, 57, and 58 in different tRNAs. In some cases, these modifications have been shown to increase tRNA structural stability and induce correct tRNA folding. This review provides an overview of the currently known m1A modifications, the different m1A modification sites, the biological role of each modification, and the enzyme responsible for each methylation in different species. The review further describes, in detail, two enzyme families responsible for formation of m1A at nucleotide position 9 and 58 in tRNA with a focus on the tRNA binding, m1A mechanism, protein domain organisation and overall structures.
1-Methyladenosine (m 1 A) is a modified nucleoside found at positions 9, 14, 22 and 58 of tRNAs, which arises from the transfer of a methyl group onto the N1-atom of adenosine. The yqfN gene of Bacillus subtilis encodes the methyltransferase TrmK ( Bs TrmK) responsible for the formation of m 1 A 22 in tRNA. Here, we show that Bs TrmK displays a broad substrate specificity, and methylates seven out of eight tRNA isoacceptor families of B. subtilis bearing an A 22 . In addition to a non-Watson–Crick base-pair between the target A 22 and a purine at position 13, the formation of m 1 A 22 by Bs TrmK requires a full-length tRNA with intact tRNA elbow and anticodon stem. We solved the crystal structure of Bs TrmK showing an N-terminal catalytic domain harbouring the typical Rossmann-like fold of Class-I methyltransferases and a C-terminal coiled-coil domain. We used NMR chemical shift mapping to drive the docking of Bs tRNA Ser to Bs TrmK in complex with its methyl-donor cofactor S-adenosyl-L-methionine (SAM). In this model, validated by methyltransferase activity assays on Bs TrmK mutants, both domains of Bs TrmK participate in tRNA binding. Bs TrmK recognises tRNA with very few structural changes in both partner, the non-Watson–Crick R 13 –A 22 base-pair positioning the A 22 N1-atom close to the SAM methyl group.
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