Selective and reversible inhibition of initiation of protein synthesis in mammalian cells

Hypertonicity effected by elevation of NaCl concentration in the growth medium results in a rapid cessation of protein synthesis in HeLa cells accompanied by a complete breakdown of polyribosomes. Since elongation and termination of polypeptide synthesis proceeds normally, it is concluded that elevated NaCl concentration in the medium selectively inhibits the initiation of peptide chain formation. Pulse-labeling of poliovirus-infected cells at different times after incubation of the cells in hypertonic medium can be used to map the poliovirus genome. Upon restoration of isotonicity re-initiation of protein synthesis occurs only at the proper initiation site and synthesis proceeds at a normal rate. This synchronized re-initiation of protein synthesis observed upon restoration of isotonicity, in turn, allowed us to determine the gene sequence of poliovirus RNA in a novel way.