Control of Haemoglobin Synthesis

Abstract

The distribution of ribosomes along the mRNAs for α and β chains was measured in cells which had achieved a steady state of protein synthesis after incubation with haem and iron or with the iron‐chelating agent 2,2′‐dipyridyl. The distribution was found to be uniform under both conditions for the α and β chain mRNAs, despite the dramatic breakdown of polysomes observed in the presence of dipyridyl. Since a uniform distribution of ribosomes along an mRNA indicates the absence of rate‐limiting steps in chain elongation or chain termination, we conclude that the slowing of protein synthesis during iron deprivation is not caused by the introduction of rate‐limiting steps into these processes. In the presence of dipyridyl the total numbers of ribosomes synthesising α and β chains were reduced to roughly the same extent indicating that iron starvation inhibits the synthesis of both α and β chains. In order to confirm that the rate chain elongation was not altered during iron starvation, we attempted to compare the rates of translation of the two mRNAs in the presence and absence of iron. Some of the difficulties in measuring the translation times for the α and β chain mRNAs under conditions of iron deprivation are discussed. Under conditions where a partial effect of iron deprivation was evident, we showed that the rate of translation of both α and β chain mRNAs was essentially unchanged. Both sets of findings support the hypothesis that, in vivo, the availability of haem controls the process of chain initiation.