EFFECT OF A MUTATION IN THE ANTICODON OF HUMAN MITOCHONDRIAL TRNA(PRO) ON ITS POSTTRANSCRIPTIONAL MODIFICATION PATTERN

Although the gene sequences of all 22 tRNAs encoded in the human mitoc hondrial genome are known, little information exists about their seque nces at the RNA level, This becomes a crucial limitation when searchin g for a molecular understanding of the growing number of maternally in herited human diseases correlated with point mutations in tRNA genes, Here we describe the sequence of human mt-tRNA(Pro) purified from plac enta, It shows absence of editing events in this tRNA and highlights t he presence of eight post-transcriptional modifications, These include T54, never found so far in an animal mt-tRNA, and m(1)G37, a modifica tion known to have fundamental functional properties in a number of ca nonical tRNAs, Occurrence of m(1)G37 was further investigated in an an alysis of the substrate properties of in vitro transcripts of human mt -tRNA(Pro) towards pure Escherichia coil 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 nucleot ide for methylation, Since mutation of nt 36 was shown to be correlate d with myopathy, the potential consequences of nonmodification or unde r-modification of mt-tRNA nucleotides in expression of the particular myopathy and of mitochondrial diseases in general are discussed.