Effect of a mutation in the anticodon of human mitochondrial tRNAPro on its post-transcriptional modification pattern

Nucleic Acids Res. 1998 Jan 15;26(2):537-43. doi: 10.1093/nar/26.2.537.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticodon*
  • Base Sequence
  • Escherichia coli / enzymology
  • Humans
  • Methylation
  • Methyltransferases / metabolism
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Conformation
  • Placenta / chemistry
  • RNA / chemistry*
  • RNA / metabolism
  • RNA Editing
  • RNA Processing, Post-Transcriptional*
  • RNA, Mitochondrial
  • RNA, Transfer, Pro / chemistry*
  • RNA, Transfer, Pro / metabolism
  • Structure-Activity Relationship
  • tRNA Methyltransferases*


  • Anticodon
  • RNA, Mitochondrial
  • RNA, Transfer, Pro
  • RNA
  • Methyltransferases
  • tRNA Methyltransferases
  • tRNA (guanine-N1-)-methyltransferase