High Stability of Messenger RNA in Growing Cultured Cells

Abstract

THE discovery that messenger RNA (mRNA) in mammalian cells contains sequences of polyadenylic acid (poly A) about 200 nucleotides long localized at the 3′-OH terminus of the mRNA molecule^1–5 has raised questions about the function of poly A, but has also provided a powerful new tool for the study of mRNA metabolism. I have measured the stability of mRNA in exponentially growing mouse L-cells without having to resort to the use of inhibitors of RNA synthesis, and found that poly A-containing mRNA has a half-life of 10 h, and thus turns over approximately once per cell generation (15 h). This high stability is in striking contrast to the 3–4 h half-life for mRNA in cultured cells obtained by following the decay of polyribosomes after treatment with a high dose of actinomycin D^6,7, This, however, agrees with the finding of Cheevers and Sheinin⁸ that there is a long-lived fraction of mRNA in cells treated with a low dose of actinomycin D. Singer and Penman⁹ have simultaneously found that poly A-containing mRNA in HeLa cells turns over about once per cell generation.