title: Effect of a mutation in the anticodon of human mitochondrial tRNAPro on its post-transcriptional modification pattern.
abstract: Although the gene sequences of all 22 tRNAs encoded in the human mitochondrial genome are known, little information exists about their sequences at the RNA level. This becomes a crucial limitation when searching for a molecular understanding of the growing number of maternally inherited human diseases correlated with point mutations in tRNA genes. Here we describe the sequence of human mt-tRNAPropurified from placenta. It shows absence of editing events in this tRNA and highlights the presence of eight post-transcriptional modifications. These include T54, never found so far in an animal mt-tRNA, and m1G37, a modification known to have fundamental functional properties in a number of canonical tRNAs. Occurrence of m1G37 was further investigated in an analysis of the substrate properties of in vitro transcripts of human mt-tRNAProtowards pure Escherichia coli methylguanosine transferase. This enzyme properly methylates G37 in mt-tRNA and is sensitive to the presence of a second G at position 36, neighboring the target nucleotide for methylation. Since mutation of nt 36 was shown to be correlated with myopathy, the potential consequences of non-modification or under-modification of mt-tRNA nucleotides in expression of the particular myopathy and of mitochondrial diseases in general are discussed.
authors.affiliation: Unité Propre de Recherche 9002, 'Structure des Macromolcules Biologiques et Mécanismes de Reconnaissance', Institut de Biologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique, Strasbourg, France.
authors.forename: H
authors.initials: H
authors.lastname: Brulé
authors.forename: W M
authors.initials: WM
authors.lastname: Holmes
authors.forename: G
authors.initials: G
authors.lastname: Keith
authors.forename: R
authors.initials: R
authors.lastname: Giegé
authors.forename: C
authors.initials: C
authors.lastname: Florentz
mesh_terms: D000926:Anticodon; D001483:Base Sequence; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010920:Placenta / Q000737:chemistry; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D017393:RNA Editing; D012323:RNA Processing, Post-Transcriptional; D000077278:RNA, Mitochondrial; D012361:RNA, Transfer, Pro / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D012359:tRNA Methyltransferases
chemical_list: D000926:Anticodon; D000077278:RNA, Mitochondrial; D012361:RNA, Transfer, Pro; D012313:RNA; D008780:Methyltransferases; D012359:tRNA Methyltransferases; C036950:tRNA (guanine-N1-)-methyltransferase