Methylation of ribosomal RNA as a possible factor in cell differentiation.

The mammalian 5.8S ribosomal RNA (rRNA) contains a 2'-O-methylated uridylic acid residue which is methylated in the cytoplasm of normal tissues but is highly undermethylated in the newly synthesized RNA of rapidly growing neoplastic tissues (R. N. Nazar, T. O. Sitz, and K. D. Somers, J. Mol. Biol., 142: 117-121, 1980). To further assess the significance of these differing levels of methylation, new assays have been developed and used to analyze the steady state levels of methylation in several tissues of varied mitotic activity and degree of cellular differentiation. The results indicate that the total population of 5.8S rRNA is also undermethylated in tumor tissues and the low levels of 2'-O-methyluridylic acid which were observed in previous studies are not simply due to a slow cytoplasmic methylation process. A substantial increase in mitotic activity, as observed in regenerating rat liver, appears not to result in a general demethylation of the 5.8S rRNA but, in contrast, when rapidly dividing cells such as muscle myoblasts differentiate in vitro into postmitotic multinucleated muscle fibers, the existing 5.8S RNA population is subject to a significantly increased level of 2'-O-methylation. These data provide further evidence for the potential importance of RNA methylation in cell differentiation and tumor development.