Control of haemoglobin synthesis: Rate of translation of the messenger RNA for the α and β chains

Hunt, Tim; Hunter, Tony; Munro, Alan

doi:10.1016/0022-2836(69)90083-7

Cited by 145 publications

(41 citation statements)

References 13 publications

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“…Although Kazazian and Freedman (12) observed only small differences in the polysome distribution of rabbit nascent beta-and alphachains, Hunt and Hunter clearly determined that betachain synthesis predominates on polysomes that are heavier than those synthesizing alpha chains. In subsequent articles, Hunt, Hunter, and Munro (13,14) ascribed this finding to a faster elongation rate of alpha chains, rather than to a faster rate of initiation of beta chains, but the difficulties inherent in the measurement of elongation rate did not permit this conclusion to be drawn unambiguously. Furthermore, studies in our laboratory performed on rabbit, and most recently on human, reticulocytes have provided strong evidence that the rate of initiation of translation of betachain messenger exceeds that of alpha-chain messenger.…”

Section: Discussionmentioning

confidence: 99%

Beta Thalassemia and Translation of Globin Messenger RNA

Nathan

Lodish

Kan³

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

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To define the quality and relative quantity of beta and alpha messenger RNA in human nonthalassemic and thalassemic reticulocytes, intact cells were incubated with [35S]methionine. The relative amounts of beta-and alpha-nascent chains on polysomes of different sizes were measured by tryptic digestion of pooled polysomes and by determination of the specific activities of beta and alpha peptides that contain methionine. Betachain synthesis predominated on heavy polysomes in nonthalassemic, as well as in thalassemic cells. Since beta chains in thalassemia are made on normal-size polyribosomes, we conclude that the defect in thalassemia does not involve reduction in the rate of initiation of translation due to the production of an abnormal beta message. Such would lead to beta-chain synthesis on very small polysomes. We therefore suggest that the decreased production of beta-globin chains results from a decreased amount of functional beta-globin messenger RNA.

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Section: Discussionmentioning

confidence: 99%

Beta Thalassemia and Translation of Globin Messenger RNA

Nathan

Lodish

Kan³

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

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“…10, 16, 37, 43, 95, and 106). The first steps involve a and b globin gene translation, which takes place on the order of a few minutes per subunit (25,51,63,72,73). Given that a helices and other structural features are capable of forming spontaneously in less than a few microseconds (30,36,41,111), it is plausible that a and b chains could acquire some of their secondary and tertiary structure co-translationally.…”

Section: Pathways For Hemoglobin Assembly In Vivo and In Vitromentioning

confidence: 99%

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

Mollan

Weiss

et al. 2010

Antioxidants & Redox Signaling

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Hemoglobin biosynthesis in erythrocyte precursors involves several steps. The correct ratios and concentrations of normal alpha (a) and beta (b) globin proteins must be expressed; apoproteins must be folded correctly; heme must be synthesized and incorporated into these globins rapidly; and the individual a and b subunits must be rapidly and correctly assembled into heterotetramers. These events occur on a large scale in vivo, and dysregulation causes serious clinical disorders such as thalassemia syndromes. Recent work has implicated a conserved erythroid protein known as Alpha-Hemoglobin Stabilizing Protein (AHSP) as a participant in these events. Current evidence suggests that AHSP enhances a subunit stability and diminishes its participation in harmful redox chemistry. There is also evidence that AHSP facilitates one or more early-stage post-translational hemoglobin biosynthetic events. In this review, recent experimental results are discussed in light of several current models describing globin subunit folding, heme uptake, assembly, and denaturation during hemoglobin synthesis. Particular attention is devoted to molecular interactions with AHSP that relate to a chain oxidation and the ability of a chains to associate with partner b chains. Antioxid. Redox Signal. 12, 219-232.

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“…It is worth bearing in mind that in a situation where initiation frequency was already decreased fivefold, and thus protein output would be fivefold reduced with the repressed mRNA located in very small polysomes, superimposing an approximately fourfold decrease in elongation rate would result in little additional reduction in reporter protein output, even though the target mRNA would move into larger polysomes. For a fuller discussion of the relationship between protein output rates, polysome size, initiation frequency, and elongation rate, under steady-state conditions likely to pertain in transfected cell assays, the reader is referred to Hunt et al (1968Hunt et al ( , 1969. ]…”

Section: Conclusion That Can Be Drawn From the In Vitro Recapitulatimentioning

confidence: 99%

MicroRNAs repress translation of m⁷Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation

Standart¹,

Jackson²

2007

Genes Dev.

118

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Control of haemoglobin synthesis: Rate of translation of the messenger RNA for the α and β chains

Cited by 145 publications

References 13 publications

Beta Thalassemia and Translation of Globin Messenger RNA

Beta Thalassemia and Translation of Globin Messenger RNA

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

MicroRNAs repress translation of m⁷Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation

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Control of haemoglobin synthesis: Rate of translation of the messenger RNA for the α and β chains

Cited by 145 publications

References 13 publications

Beta Thalassemia and Translation of Globin Messenger RNA

Beta Thalassemia and Translation of Globin Messenger RNA

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation

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MicroRNAs repress translation of m⁷Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation