EMBRYONIC HEMOGLOBIN SYNTHESIS
%
of ribosome bound complete/incomplete polypeptide chains for both the
a- and ß-chains of rabbit reticulocytes. No complete ß-chains are found
on ribosomes, but a complete «-chain is found for every 5 or 6 growing
«-chains. This directly supports the supposition that ß-chains participate
in the release or completion of «-chains.
Genetic and biochemical evidence from a large number of other human
Hb mutations also suggests that nongenic levels of regulation may exist.
In hétérozygotes (e.g., HbA/Hb sickle) the amount of normal HbA
almost always predominates over the amount of mutant Hb, a fact
strongly suggestive of nongenic regulation. The rate of destruction of a
given Hb type, as well as the stability of a given message or the rate
at which it is translated into polypeptides are possible regulation sites.
Much of this data has recently been analyzed by Boyer et al. (1964)
and Zuckerandl (1964).
The messenger-ribosome complex of the erythrocyte is usually composed of several ribosomes attached to a common strand of messenger
RNA, the whole complex being called the polysome. The polysome is
the predominant site of Hb synthesis in the reticulocyte (and other
stages) (Marks et al, 1962; Gierer, 1963; Warner et al, 1962). Polysomes containing 2-6 ribosomes are the most active in Hb synthesis.
Rifkind et al. (1964) have correlated the polyribosome content, size
distribution, and total ribosome content of the cells with the rate of Hb
synthesis, both by electron microscopic and biochemical techniques.
Ribosomes of nucleated erythroid cells of the rabbit synthesize Hb at
a fast rate, and virtually all ribosomes are in polysomes. As the nucleus
is lost and the maturing red blood cell is released into the circulation,
the rate of Hb synthesis decreases, the total ribosome content falls, and
a decrease in the number and size of polysomes occurs. These findings
led Marks to propose that the decrease in ribosomes and proportion of
polysomes were responsible for the decreasing rate of Hb synthesis
during erythrocyte maturation.
Glowacki and Millette (1965) found that the total ribosome content
of mature reticulocytes was very much lower than in immature stages,
but they did not find a precipitous drop in the proportion of polysomes
present. This could be due to differences in technique, or perhaps to the
variations in serum iron present in phenylhydrazine anemias, as pointed
out by Waxman and Rabinovitz (1965b) ; iron may play a role in
maintenance of polyribosome structure.
Marks et al (1965) attempted to reconstruct the dependence of Hb
synthesis on polysomes by use of NaF. Reticulocytes which are exposed
to NaF lose their polysomes and ability to form Hb, but the effect is
reversible; washing the cells leads to restoration of polysome structure
and Hb synthesis in the absence of RNA synthesis. The correspondence
%
of ribosome bound complete/incomplete polypeptide chains for both the
a- and ß-chains of rabbit reticulocytes. No complete ß-chains are found
on ribosomes, but a complete «-chain is found for every 5 or 6 growing
«-chains. This directly supports the supposition that ß-chains participate
in the release or completion of «-chains.
Genetic and biochemical evidence from a large number of other human
Hb mutations also suggests that nongenic levels of regulation may exist.
In hétérozygotes (e.g., HbA/Hb sickle) the amount of normal HbA
almost always predominates over the amount of mutant Hb, a fact
strongly suggestive of nongenic regulation. The rate of destruction of a
given Hb type, as well as the stability of a given message or the rate
at which it is translated into polypeptides are possible regulation sites.
Much of this data has recently been analyzed by Boyer et al. (1964)
and Zuckerandl (1964).
The messenger-ribosome complex of the erythrocyte is usually composed of several ribosomes attached to a common strand of messenger
RNA, the whole complex being called the polysome. The polysome is
the predominant site of Hb synthesis in the reticulocyte (and other
stages) (Marks et al, 1962; Gierer, 1963; Warner et al, 1962). Polysomes containing 2-6 ribosomes are the most active in Hb synthesis.
Rifkind et al. (1964) have correlated the polyribosome content, size
distribution, and total ribosome content of the cells with the rate of Hb
synthesis, both by electron microscopic and biochemical techniques.
Ribosomes of nucleated erythroid cells of the rabbit synthesize Hb at
a fast rate, and virtually all ribosomes are in polysomes. As the nucleus
is lost and the maturing red blood cell is released into the circulation,
the rate of Hb synthesis decreases, the total ribosome content falls, and
a decrease in the number and size of polysomes occurs. These findings
led Marks to propose that the decrease in ribosomes and proportion of
polysomes were responsible for the decreasing rate of Hb synthesis
during erythrocyte maturation.
Glowacki and Millette (1965) found that the total ribosome content
of mature reticulocytes was very much lower than in immature stages,
but they did not find a precipitous drop in the proportion of polysomes
present. This could be due to differences in technique, or perhaps to the
variations in serum iron present in phenylhydrazine anemias, as pointed
out by Waxman and Rabinovitz (1965b) ; iron may play a role in
maintenance of polyribosome structure.
Marks et al (1965) attempted to reconstruct the dependence of Hb
synthesis on polysomes by use of NaF. Reticulocytes which are exposed
to NaF lose their polysomes and ability to form Hb, but the effect is
reversible; washing the cells leads to restoration of polysome structure
and Hb synthesis in the absence of RNA synthesis. The correspondence