The Concept of Messenger RNA and Cytodifferentiation

Synopsis. The messenger RNA hypothesis serves as a concrete model of gene function which may be of real use to the developmental biologist. The hypothesis posits that the product of a gene is an RNA molecule with a base sequence complementary to the sequence of nucleotide bases in the DNA. The operations and restrictions which define a messenger are discussed. Animal and embryonic cells, while conforming in general to the predictions, display certain variations from the original hypothesis, such as difficulties in obtaining directed synthesis of protein in vitro, greater stability of the messenger RNA, association of active ribosomes with lipoprotein membranes, and a possible heterogeneity of ribosomes. Some recent studies on messenger RNA in sea urchins and frog embryos are dis? cussed, with special reference to the nature and importance of the RNA synthesized during cleavage, the significance of new ribosome synthesis, and the potential impor? tance of control mechanisms at the translational level for regulation of new protein synthesis. The latter point is illustrated further by a discussion of the initiation of synthesis of hemoglobin in the chick embryo. The application of drugs and antimetabolites which derange and inhibit RNA synthesis (actinomycin, 8-azaguanine, 5-fluorouracil, and 5-bromodeoxyuridine) shows that 8 hours prior to its onset, the synthesis of hemoglobin is independent of the synthesis of RNA of high molecular weight. The initiation of hemoglobin synthesis is probably regulated at the translational level. Preliminary experiments using the heme precursor, delta-amino-levulinic acid, show that heme may be limiting for the onset of hemoglobin synthesis.