Methyldeficient mammalian 4s RNA: evidence for L-ethionine-induced inhibition of N6-dimethyladenosine synthesis in rat liver tRNA.
The nucleotide composition of 4s RNA from livers of rats fed with a diet containing 0.3% D-ethionine was found to be identical with that from untreated animals. In contrast, one single modified nucleotide was absent in 4s RNA from livers of rats fed with a 0.3% L-ethionine diet. The minor nucleo=tide was also absent in liver 4s RNA from rats fed with a 0.3% L-ethionine diet followed by ten days of normal food. It was identified after dephosphorylation by ultraviolet absorption spectra, cochromatography with authentic material and mass spectra as N(6)-dimethyladenosine. It is concluded that S-adenosylethionine, the primary product of L-ethionine in the liver, causes strong and selective inhibition of the specific RNA-methylase responsible for adenosine to N(6)-dimethyl=adenosine methylation in rat liver 4s RNA. Compared to the strong inhibition of N(6)-dimethyladenosine formation described here, L-ethionine-dependent ethylation of liver 4s RNA is far less efficient. The quantitation of l-methyladenosine, ribothymidine and 3'-terminal adenosine in this 4s RNA as well as its aminoacid acceptor activity is typical for tRNA; hence it may be concluded that N(6)-dimethyladenosine is a component of rat liver tRNA. This may demonstrate the first evidence for the existence of specifically methyl-deficient mammalian tRNA. A possible correlation between the activity of L-ethionine as a liver carcinogen and its ability to induce the formation of methyl-deficient tRNA by selectively inhibiting the synthesis of N(6)-dimethyladenosine on the tRNA level in the same organ is discussed.
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002250:Carbon Radioisotopes; D002854:Chromatography, Paper; D002855:Chromatography, Thin Layer; D005001:Ethionine / Q000494:pharmacology*; D005260:Female; D007536:Isomerism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D013058:Mass Spectrometry; D000432:Methanol; D008745:Methylation; D009841:Oligonucleotides / Q000032:analysis; D012343:RNA, Transfer / Q000096:biosynthesis; D051381:Rats; D012260:Ribonucleases; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D002250:Carbon Radioisotopes; D009841:Oligonucleotides; D012343:RNA, Transfer; D012260:Ribonucleases; D000241:Adenosine; D005001:Ethionine; D000432:Methanol