The Effects of Growth Factors on tRNA^Lys Modification

Abstract

One of the more interesting questions in tRNA research is whether the redundancy of tRNA isoaccepting species has any functional meaning. Numerous reports have indicated that the distributions of these isoaccepting tRNA species are altered under different physiological conditions (Sueoka and Kano-Sueoka 1970; Littauer and Inouye 1973). The multiplicity of isoaccepting tRNA species seen in living cells suggests that these species may arise as a result of differences in base modification, which may play a role in regulating tRNA function (Agris and Söll 1977). Several laboratories have shown that RPC-5 chromatography can resolve tRNA^Lys into three to nine isoaccepting species (Ortwerth and Liu 1973; Juarez et al. 1974; Katze 1975). All these species, however, share only two code words, AAA and AAG (Ortwerth et al. 1973; Rudloff and Hilse 1975). One of the tRNA^Lys isoacceptors, tRNA4^Lys, has been proposed as being a requirement for cell division (Ortwerth and Liu 1973). This tRNA is present in all tissues and cultured cells which have the ability to divide, but absent in tissues which have become terminally differentiated. Furthermore, the level of this tRNA correlated exactly with the doubling time of cells in culture (Conlon-Hollingshead and Ortwerth 1980). The levels of this tRNA remained high during log growth in Balb/c 3T3 cells, but decreased sharply just before the cells became confluent. Upon trypsinization and replating, the levels of this tRNA rose immediately and reached log growth levels before the cells began to divide. These alterations in tRNA^Lys isoacceptors may be due to the modulation of the activity of certain tRNA modification enzymes brought about by cell density, medium depletion, or serum factors.

The authors would like to thank Dr. Orchid Chu-Der for providing the LM-cell tRNA^Lys and Mary Harrison for her excellent work on the isolation of purified tRNA^Lys species. This work was supported in part by USPHS Grant Ca-26423 and in part by the Eye Research Foundation of Missouri, Inc.