H. Grosjean et al., ENZYMATIC CONVERSION OF ADENOSINE TO INOSINE AND TO N-1-METHYLINOSINEIN TRANSFER-RNAS - A REVIEW, Biochimie, 78(6), 1996, pp. 488-501
Inosine (6-deaminated adenosine) is a characteristic modified nucleosi
de that is found at the first anticodon position (position 34) of seve
ral tRNAs of eukaryotic and eubacterial origins, while N-1-methylinosi
ne is found exclusively at position 37 (3' adjacent to the anticodon)
of eukaryotic tRNA(Ala) and at position 57 (in the middle of the Psi l
oop) of several tRNAs from halophilic and thermophilic archaebacteria.
Inosine has also been recently found in double-stranded RNA, mRNA and
viral RNAs. As for all other modified nucleosides in RNAs, formation
of inosine and inosine derivative in these RNA is catalysed by specifi
c enzymes acting after transcription of the RNA genes. Using recombina
nt tRNAs and T gamma-runoff transcripts of several tRNA genes as subst
rates, we have studied the mechanism and specificity of tRNA-inosine-f
orming enzymes. The results show that inosine-34 and inosine-37 in tRN
As are both synthesised by a hydrolytic deamination-type reaction, cat
alysed by distinct tRNA:adenosine deaminases. Recognition of tRNA subs
trates by the deaminases does not strictly depend on a particular 'ide
ntity' nucleotide. However, the efficiency of adenosine to inosine con
version depends on the nucleotides composition of the anticodon loop a
nd the proximal stem as well as on 3D-architecture of the tRNA. In euk
aryotic tRNA(Ala), N-1-methylinosine-37 is formed from inosine-37 by a
specific SAM-dependent methylase, while in the case of N-1-methylinos
ine-57 in archaeal tRNAs, methylation of adenosine-57 into N-1-methyla
denosine-57 occurs before the deamination process The T Psi-branch of
fragmented tRNA is the minimalist substrate for the N-1-methylinosine-
57 forming enzymes. Inosine-34 and N-1-methylinosine-37 in human tRNA(
Ala) are targets for specific autoantibodies which are present in the
serum of patients with inflammatory muscle disease of the PL-12 polymy
ositis type. Here we discuss the mechanism, specificity and general pr
operties of the recently discovered RNA:adenosine deaminases/editases
acting on double-stranded RNA, intron-containing mRNA and viral RNA in
relation to those of the deaminases acting on tRNAs.