TRNA methyltransferase studies

S-adenosylmethionine tRNA methyltransferases have been shown to occur in all kind of cells so far studied, both prokaryote and eukaryote. In eukaryote cells they are mostly localized in the cytosol and mitochondria recent results show the presence of these enzymes in nuclei of mouse L-cells and of Xenopus oocyte l. These latter results suggest that the intracellular localization of such enzymes should be more accurately investigated by the refined techniques now available. The possible localization of these enzymes within the nuclei is of interest if visualized in connection with the timing and the place of tRNA maturation events. 

The molecular size of the four methylase activities isolated from S.typhimurium was studied by comparing their sedimentation profile with that of proteins of known molecular weight. Results obtained show that four tRNA methylases have a Mj- ranging from 25,000 to 65,000 daltons, except the enzyme preparation mentioned above as no. 1, which shows also an aggregate form of higher (120,000). All the other tRNA methyltransferases isolated so far from other sources appear to have higher. ... 

Adenosylhomocysteine (Ado-Hcy) is the first studied and the most active inhibitor of tRNA methyltransferases, both from... 

A second group of SAM-dependent methylases acts on much larger substrates, such as proteins and nucleic acids (9). Only recently has progress been made on isolating purified proteins which methylate macromolecules such as tRNA (10), mRNA (11), and proteins (12). In the case of tRNA (adenine-1)-methyltransferase (E.C. 2.1.1.36) (10a) and protein carboxyl-0-methyltransferase (E.C. 2.1.1.24) (13), kinetic studies are consistent with the random sequential reaction proposed for COMT, and thus suggest a direct methyl transfer in the ternary complex. One enzyme which does not show kinetics consistent with a direct methyl transfer is histamine-N-rnethyltransferase (E. C. 2.1.1.8) (14). The data reported are consistent with a double—displacement mechanism of... 

After briefly reviewing the modifications by S-adenosylmethi-onine of DNA, mRNA and rRNA, the Authors discuss the methylation of tRNA, and report the most significant data on its role in the cellular functions of tRNA. In particular, the authors summarize some results from their laboratory concerning kinetic studies on the effect of adenosylhomocysteine and several thioester analogs on tRNA(guanine-7)-methyltransferase, and concerning a fast procedure to purify this enzyme from S.typhimurium. 

Analogs of metabolic intermediates have been widely used to investigate the mechanism of biochemical reactions. Along this line, a series of sulfonium compounds and thioethers, analogs of S-adeno-syl-L-methionine and S-adenosyl-L-homocysteine respectively have been assayed as substrate and/or inhibitors of methyltransfer reactions (33-36). However, these studies mainly concerned with methyltransferases acting on small molecules and tRNA (33-37). In this brief account, we have reviewed recent studies on the effect of afore-mentioned compounds on various protein-specific methyltransferases. 

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