The genetic control of protein synthesis: The haemoglobin model

The major steps in haemoglobin synthesis in red cell precursors are now worked out and only details of specific mechanisms remain to be filled in. Thus the major steps in the production of a globin chain are the transcription of large-molecular-weight precursor mRNA (Hn RNA) from the appropriate gene, the cleavage of Hn RNA to produce definitive template mRNA which diffuses into the cell cytoplasm, the processes of chain initiation, translation, and termination, and finally the association of subunits to form a stable tetramer. From what little information there is it appears that this complex series of events is controlled at several levels but that the major control mechanisms are mediated in the processes of transcription rather than translation. There is increasing evidence that the chromatin proteins, particularly the acidic proteins, have specific functions in maintaining areas of DNA repressed and the activation of the haemoglobin loci results from complex interactions with external inducers, the nature of which is not yet known. Virtually nothing is known about the factors involved in the switch from the intrauterine to adult haemoglobins although this appears to be a coordinated event throughout the erythropoietic tissue of the fetus. The isolation and characterization of human mRNA has made possible both the study of the function of thalassaemic mRNA in heterologous systems and , more recently, its quantitation in abnormal red-cell precursors. Furthermore the ability to make cDNA using viral re verse transcriptase has made possible the estimation of the number of haemoglobin genes, both in normal human subjects and in those with different forms of thalassaemia and other genetic disorders of haemoglobin production.