Globin Messenger RNA in Hemoglobin H Disease

Functional messenger RNA (mRNA) for human globin synthesis was isolated from reticulocytes of each of two patients with hemoglobin H disease. The RNA was tested for its capacity to direct globin synthesis in a messenger RNA-dependent cell-free system derived from Krebs Type II mouse ascites tumor cells. In each case, hemoglobin H disease mRNA directed the synthesis of a great excess of β-globin chains relative to α-globin chains of hemoglobin A. The β/αsynthetic ratios obtained in the cell-free system at saturating concentrations of mRNA were >22 and > 15, respectively, for the two hemoglobin H disease mRNA preparations, whereas the β/αsynthetic ratios obtained by incubation of intact reticulocytes from these same patients were 2.6 and 2.8, respectively. The β/αsynthetic ratio obtained in the cell-free system did not vary when lower concentrations of hemoglobin H disease mRNA were used. A marked decrease in the amount of functional α-globin-chain mRNA relative to β-chain mRNA is therefore associated with the decreased α-chain synthesis observed in hemoglobin H disease. This decrease in α-chain-specific mRNA activity is greater than expected from the β/asynthetic ratio of intact reticulocytes in hemoglobin H disease.