Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA).
A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation.
D001358:Avian Sarcoma Viruses; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002474:Cell-Free System; D003839:Deoxyadenosines / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D008715:Methionine / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology*; D012359:tRNA Methyltransferases / Q000037:antagonists & inhibitors*
D003839:Deoxyadenosines; D013872:Thionucleosides; C013919:5'-deoxy-5'-S-isobutylthioadenosine; D012343:RNA, Transfer; D012435:S-Adenosylhomocysteine; D008715:Methionine; D012359:tRNA Methyltransferases