Quantitative Correlation between Globin mRNAs and Synthesis of Fetal and Adult Hemoglobins during Hemoglobin Switchover in the Perinatal Period

To determine whether a quantitative relationship existed between globin mRNAs and their translation products during the period of switchover, the relative amounts of the mRNAs of α-, β-, and γ-globins and their protein synthesis in cord blood samples were measured and compared. The synthesis of globins in immature red cells was measured by the incorporation of [3H]leucine followed by separation and quantitation of the polypeptides on a C4-reverse phase HPLC. The relative proportions of the mRNAs of globins were determined by RNase protection assay. A comparison of cord blood samples from 45 newborn infants of different gestational ages(25-41 wk; birth weight, 850-4695 g) revealed a very significant correlation(r2 = 0.924) between the ratio of globin mRNAs encoding HbF([γ/(γ + β)] mRNAs) and HbA ([β/(γ + β)] mRNAs) and the ratio of de novo synthesis of HbF [γ/(γ +β)] and HbA [β/(γ + β)]. There was a linear relationship between the proportions of globin mRNAs encoding HbF with the proportional synthesis of HbF throughout the developmental stage studied. The ratio ofα2/α1-globin mRNAs increased from 2.0 ± 0.2 between 24 and 36 wk of gestation to 2.3 ± 0.4 (p = 0.02) during 37-41 wk of gestation. These results of the complementary changes atα- and β-loci during fetal development may further the understanding of the coordinated regulation of globin gene expression.