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Mitochondrial tRNAs are transcribed as long polycistronic transcripts of precursor tRNAs and undergo posttranscriptional modifications such as endonucleolytic processing and methylation required for their correct structure and function. Among them, 5'-end processing and purine 9 N1-methylation of mitochondrial tRNA are catalysed by two proteinaceous complexes with overlapping subunit composition. The Mg2+-dependent ribonuclease P complex for 5'-end cleavage comprises the methyltransferase domain-containing protein TRMT10C/MRPP1, short-chain oxidoreductase HSD17B10/MRPP2, and metallonuclease KIAA0391/MRPP3. An MRPP1-MRPP2 sub-complex also catalyses the formation of 1-methyladenosine/1-methylguanosine at position 9 using S-adenosyl-L-methionine as methyl donor. However, a lack of structural information has precluded insights into how these complexes methylate and process mitochondrial tRNA. Here, we used a combination of X-ray crystallography, interaction and activity assays, and small angle X-ray scattering (SAXS), to gain structural insight into the two tRNA modification complexes and their components. The MRPP1 N-terminus is involved in tRNA binding and monomer-monomer self-interaction, while the C-terminal SPOUT fold contains key residues for S-adenosyl-L-methionine binding and N1-methylation. The entirety of MRPP1 interacts with MRPP2 to form the N1-methylation complex, while the MRPP1-MRPP2-MRPP3 ribonuclease P complex only assembles in the presence of precursor tRNA. This study proposes low-resolution models of the MRPP1-MRPP2 and MRPP1-MRPP2-MRPP3 complexes that suggest the overall architecture, stoichiometry, and orientation of subunits and tRNA substrates.

Original publication




Journal article


The Journal of biological chemistry

Publication Date



Structural Genomics Consortium, University of Oxford, United Kingdom.