The Concept of Messenger RNA and Cytodifferentiation

The messenger RNA hypothesis serves as a concrete model of genefunction which may be of real use to the developmental biologist.The hypothesis posits that the product of a gene is an RNA moleculewith a base sequence complementary to the sequence of nucleotidebases in the DNA. The operations and restrictions which definea messenger are discussed. Animal and embryonic cells, whileconforming in general to the predictions, display certain variationsfrom the original hypothesis, such as difficulties in obtainingdirected synthesis of protein in vitro, greater stabilityofthe messenger RNA, association of active ribosomes with lipoproteinmembranes, and a possible heterogeneity of ribosomes. Some recent studies on messenger RNA in sea urchins and frogembryos are discussed, with special reference to the natureand importance of the RNA synthesized during cleavage, the significanceof new ribosome synthesis, and the potential importance of controlmechanisms at the 'translational level for regulation of newprotein synthesis The latter point is illustrated further by a discussion of theinitiation of synthesis of hemoglobin in the chick embryo. Theapplication of drugs and antimetabolites which derange and inhibitRNA synthesis (actinomycin, 8-azaguanine, 5-fluorouracil, and5-bromodeoxyuridine) shows that 8 hours prior to its onset,the synthesis of hemoglobin is independent of the synthesisof RNA of high molecular weight. The initiation of hemoglobinsynthesis is probably regulated at the translational level.Preliminary experiments using the heme precursor, delta-amino-levulinicacid, show that heme may be limiting for the onset of hemoglobinsynthesis.