Alterations of transfer RNA during erythroid differentiation of murine virus-induced leukemia cells

Abstract

An investigation of transfer RNA composition during differentiation of mammalian cells was undertaken because of the reported involvement of tRNA in the regulation of protein synthesis ( Goldberger R.F. (1974) Science 183, 810–816 ). Erythroid differentiation of cells in culture was studied with murine virus-induced leukemia cells that were stimulated to differentiate by dimethyl sulfoxide. The composition of the cells' tRNA was found to change concurrently with the stimulated biosynthesis of hemoglobin. The guanylic acid content of tRNA from the differentiating leukemia cells was reduced markedly as compared with that of cells cultured in the absence of dimethyl sulfoxide. In addition, the content of the minor nucleotides ribothymidylic acid, pseudouridylic acid and ribose methylated guanylic acid in the tRNA of differentiating cells was altered compared with that of control cultures. The major and minor nucleotide compositions of tRNA from seven other cell lines (mouse and human) that do not undergo differentiation were not significantly affected when these cells were cultured in the presence of dimethylsulfoxide. At least three species of tRNA obtained from differentiating leukemia cells migrated differently in two-dimensional polyacrylamide-slab-gel electrophoresis from the tRNA of cells grown in the absence of dimethylsulfoxide. Investigation of tRNA specific for the amino acid lysine showed that the relative amounts of the various isoaccepting species changed during erythroid differentiation. Changes in the nucleotide composition of tRNA, the electrophoretic migration of tRNA species and the relative amounts of tRNA Lys isoacceptor species strongly indicate that the tRNA population of these leukemia cells was altered during dimethyl sulfoxide-stimulated erythroid differentiation.