A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase - extensive moonlighting in mitochondrial tRNA biogenesis.

Elisa Vilardo,Christa Nachbagauer,Andreas Taschner,Walter Rossmanith,Johann Holzmann,Aurélie Buzet

doi:10.1093/nar/gky931

Abstract

Transfer RNAs (tRNAs) reach their mature functional form through several steps of processing and modification. Some nucleotide modifications affect the proper folding of tRNAs, and they are crucial in case of the non-canonically structured animal mitochondrial tRNAs, as exemplified by the apparently ubiquitous methylation of purines at position 9. Here, we show that a subcomplex of human mitochondrial RNase P, the endonuclease removing tRNA 5 0 extensions, is the methyltransferase responsible for m 1 G9 and m 1 A9 formation. The ability of the mitochondrial tRNA:m 1 R9 methyltransferase to modify both purines is uncommon among nucleic acid modification enzymes. In contrast to all the related methyltransferases, the human mitochondrial enzyme, moreover, requires a short-chain dehydrogenase as a partner protein. Human mitochondrial RNase P, thus, constitutes a multifunctional complex, whose subunits moonlight in cascade: a fatty and amino acid degradation enzyme in tRNA methylation and the methyltransferase, in turn, in tRNA 5 0 end processing.

Highlights

In 2012, we reported that all three human TRM10 homologues have tRNA methyltransferase activity
In a recent follow-up study, we were not able to reproduce the reported tRNA:m1G9 methyltransferase activity of human TRMT10B with fresh enzyme preparations. This prompted us to revisit the original preparation used in 2012, and mass spectrometry analysis of the concerned TRMT10B preparation revealed a significant contamination with TRMT10A, suggesting that the tRNA:m1G9 methyltransferase activity previously observed was due to TRMT10A rather than TRMT10B
In contrast to the previously reported results, none of the 8 tested tRNA substrates was methylated by TRMT10B. It remains unclear whether TRMT10B has a more restricted substrate specificity than the other studied TRM10 homologues, has at all tRNA methyltransferase activity, or, like TRMT10C, requires (a) cofactor(s) for activity

Summary

Introduction

In 2012, we reported that all three human TRM10 homologues have tRNA methyltransferase activity. A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase – extensive moonlighting in mitochondrial tRNA biogenesis The authors wish to draw attention to an error in their published article.

Results

Conclusion