title: A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase--extensive moonlighting in mitochondrial tRNA biogenesis.
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' 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' end processing.
authors.affiliation: Center for Anatomy and Cell Biology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Elisa
authors.initials: E
authors.lastname: Vilardo
authors.forename: Christa
authors.initials: C
authors.lastname: Nachbagauer
authors.forename: Aurélie
authors.initials: A
authors.lastname: Buzet
authors.forename: Andreas
authors.initials: A
authors.lastname: Taschner
authors.forename: Johann
authors.initials: J
authors.lastname: Holzmann
authors.forename: Walter
authors.initials: W
authors.lastname: Rossmanith
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D059367:RNA Cleavage; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D043262:Ribonuclease P / Q000378:metabolism*; D012359:tRNA Methyltransferases / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D021122:Protein Subunits; D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer; D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; D008780:Methyltransferases; C578375:TRMT10c protein, human; D012359:tRNA Methyltransferases; D043262:Ribonuclease P