Trm8Trm82

Trm8Trm82 refers to the two-subunit tRNA methyltransferase complex found in eukaryotes that catalyzes the formation of N7-methylguanosine at position 46 (m7G46) in tRNA. In Saccharomyces cerevisiae and many other species, the complex consists of Trm8, the catalytic subunit, and Trm82, a non-catalytic regulatory subunit essential for activity and substrate recognition. The activity is conserved across diverse eukaryotes, with similar functional pairs identified in other organisms.

The enzymatic mechanism involves an S-adenosyl-L-methionine-dependent transfer of a methyl group to the N7 position of guanine 46 in the tRNA. Trm8 contains the catalytic motifs typical of methyltransferases, while Trm82 facilitates proper RNA binding and stabilizes the enzyme-substrate complex, enabling efficient modification of tRNA.

Biological role and significance include the stabilization and proper folding of tRNA molecules, which in turn influences translation efficiency and accuracy. M7G46 modification affects the structural properties of tRNA and can impact decoding fidelity. Loss or reduction of Trm8-Trm82 activity in yeast leads to decreased m7G46 levels, altered tRNA biogenesis, and growth defects under stress or high-temperature conditions, highlighting the complex’s role in cellular fitness.

Evolution and human relevance: The Trm8-Trm82 pair is conserved in eukaryotes. In humans, the functional homologs METTL1 (catalytic) and WDR4 (regulatory) form a METTL1-WDR4 complex that performs the analogous m7G46 modification on tRNAs, illustrating the evolutionary conservation of this modification pathway. Dysregulation of this pathway has been implicated in developmental abnormalities and disease in higher organisms.