Translation of human globin mRNA: globin synthesis in cells containing Hb
Leiden
RF Rieder and GW James
Most structurally abnormal hemoglobins are present in smaller amounts than
HbA in the erythrocytes of heterozygous subjects. In the presence of a
hemoglobinopathy, alpha and beta globin synthesis remains balanced with
equal production of the two types of chains. In reticulocytes of subjects
with Hb Leiden (beta 6 or 7 glu leads to 0) there is greater production of
alpha than beta globin in vitro (beta/alpha = 0.67), and slightly more beta
A is synthesized than beta Leiden (beta A/beta Leiden = 1.28). Differences
in specific mRNA content, rates of initiation of chain synthesis, or rates
of chain elongation could be responsible for such differential polypeptide
synthesis. In the present study, the ribosomal assembly of beta A, beta
Leiden, and alpha globin chains was examined in peripheral blood. The
translation times of the three chains did not differ significantly (average
times: beta A = 65.4 sec, beta Leiden = 70.8 sec, alpha = 53.5 sec). These
results indicated that an altered rate of translation was not the source of
the anomalous globin synthesis observed in vitro in cells containing Hb
Leiden. The experiments suggested that the observed imbalance in alpha/beta
production was due to either differential rates of initiation of globin
chain synthesis or quantitative differences in the amounts of the specific
mRNAs present in the cells.
Volume 47,
Issue 3,
pp. 489-494,
03/01/1976
Copyright © 1976 by The American Society of Hematology
