Early Hypomethylation of 2′-O-Ribose Moieties in Hepatocyte Cytoplasmic Ribosomal RNA Underlies the Protein Synthetic Defect Produced by CCl4

• Published in: The Journal of cell biology 1987-08, Vol.105 (2), p.705-711
• Main Authors: Clawson, Gary A., MacDonald, John R., Woo, C. H.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carbon; Carbon Tetrachloride - pharmacology; Carbon Tetrachloride Poisoning - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Cytoplasm - drug effects; Cytoplasm - metabolism; HeLa cells; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Messenger RNA; Methylation; Nucleosides; Protein Biosynthesis - drug effects; Protein synthesis; Rats; Rats, Inbred Strains; Ribose; Ribosomal RNA; Ribosomes; RNA; RNA, Ribosomal - drug effects; RNA, Ribosomal - genetics; Solvents; Tetrachlorides; Toxicology
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.105.2.705

Carbon tetrachloride ( CCl4) treatment of rats produces an early defect in methylation of hepatocyte ribosomal RNA, which occurs concurrently with a defect in the protein synthetic capacity of isolated ribosomes. The CCl4-induced methylation defect is specific for the 2′-O-ribose position, and a corresponding proportional increase in m7G base methylation occurs in vivo. Undermethylated ribosomal subunits (rRNA) from CCl4-treated preparations can be methylated in vitro to a much greater extent than those from control preparations, and in vitro methylation restores their functional capacity. In vitro methylation of treated ribosomal subunits (which restores functional capacity) occurs at 2′-O-ribose positions (largely G residues). In contrast, in vitro methylation of control ribosomal subunits (which does not affect functional activity) represents base methylation as m7G, sites which are apparently methylated in treated preparations in vivo. Methylation/demethylation of 2′-O-ribose sites in rRNA exposed on the surface of cytoplasmic ribosomal subunits may represent an important cellular mechanism for controlling protein synthesis in quiescent hepatocytes, and it appears that CCl4disrupts protein synthesis by inhibiting this 2′-O-ribose methylation.