Translational competition as a possible basis of modulation in retinal pigment cell cultures

A theory is suggested that new messenger RNA produced by rapidly growing primary monolayer cultures of chick retinal pigment cells competes for translation with existing tyrosinase messenger RNA and dilutes out tyrosinase synthesis. A correlation between the rapid loss of tyrosinase synthesis and an early increase in the rate of new RNA synthesis is consistent with thsi theory. Protein synthesis increases at a lower rate than RNA synthesis, and rapid DNA synthesis occurs later. When monolayer cultures become crowded, the cells begin synthesizing melanin at a more rapid rate; there is also a decrease in the rates of both RNA and protein synthesis. A persistent low level of melanin synthesis in older cultures suggests that tyrosinase genes may remain continually active and that some tyrosinase synthesis leaks through the competition barrier. Two additional observations support a translational competition theory. If new RNA synthesis in cultured cells is blocked by the inhibitor actinomycin D, then tyrosinase synthesis continues instead of almost disappearing by 12 hours of culture. Secondly, an estimate of tyrosinase messenger RNA stability, using actinomycin D, illustrates that it is more stable than is indicated by the early decrease in tyrosinase synthesis. For this reason some mechanism other than tyrosinase gene inactivation seems to be a necessary cause of the decrease in tyrosinase synthesis observed early in culture. The possibility is discussed that translational competition may occur in other examples of cellular dedifferentiation.