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 alpha-, beta-, and gamma-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 ([gamma/(gamma + beta)] mRNAs) and HbA ([beta/(gamma + beta)] mRNAs) and the ratio of de novo synthesis of HbF [gamma/(gamma + beta)] and HbA [beta/(gamma + beta)]. 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 of alpha2/alpha1-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 at alpha- and beta-loci during fetal development may further the understanding of the coordinated regulation of globin gene expression.