Cytoplasmic microinjection of immunoglobulin Gs recognizing RNA helices inhibits human cell growth

Abstract

We report here that nucleolar and cytoplasmic RNA in mammalian cells is recognized specifically by both experimentally induced monoclonal IgG unique for left-handed Z-RNA and by autoimmune mouse monoclonal IgG specific for ribosomal RNA. Nucleolar Z-RNA synthesis, like nucleolar ribosomal RNA synthesis, is inhibited by actinomycin D treatment and dimethylsulfoxide-induced differentiation. Immune anti- Z-RNA IgGs microinjected into living nuclei bind nucleolar RNA, and these complexes appear to be removed from the nucleus within minutes. Cytoplasmically microinjected monoclonal or polyclonal anti- Z-RNA IgGs specifically bind cytoplasmic RNA and inhibit cell multiplication. Microinjection of antibodies directed against double-stranded A-form RNA also inhibits cell growth, indicating physiological roles for both these double-stranded RNAs. Elevated ionic conditions, which in energy-minimized models can cause the walls of the groove in Z-RNA (but not Z-DNA) to approach each other and close, also prevent antibody binding to specific synthetic or cellular Z-RNA determinants. Our antibodies binding unique Z-RNA structures probably recognize antigens determined by the exposed 2′-OH ribose sugarphosphate groups.