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. 1970 Dec;67(4):1854–1861. doi: 10.1073/pnas.67.4.1854

Cell-Free Hemoglobin Synthesis in Beta-Thalassemia

J M Gilbert 1, A G Thornton 1, A W Nienhuis 1, W F Anderson 1
PMCID: PMC283439  PMID: 5275383

Abstract

Human ribosomes obtained from the reticulocytes of patients having either homozygous beta-thalassemia (thalassemia ribosomes) or a hematological disorder unrelated to thalassemia („normal” ribosomes) have been utilized in a cell-free system highly active in the synthesis of intact human globin chains. This system is dependent on the addition of a ribosomal wash fraction from reticulocytes that contains factors necessary for chain initiation. In response to the ribosomal wash fraction, isolated from either thalassemia, normal human, or rabbit reticulocytes, normal human ribosomes synthesize equal amounts of alpha and beta chains. In contrast, in response to all three types of ribosomal wash fractions, thalassemia ribosomes synthesize 8-times more α than β chains, a ratio similar to that produced in the intact cells of these patients. The molecular defect in beta-thalassemia, therefore, does not appear to be associated with initiation factors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bank A., Braverman A. S., O'Donnell J. V., Marks P. A. Absolute rates of globin chain synthesis in thalassemia. Blood. 1968 Feb;31(2):226–233. [PubMed] [Google Scholar]
  2. Bank A., Marks P. A. Protein synthesis in a cell free human reticulocyte system: ribosome function in thalassemia. J Clin Invest. 1966 Mar;45(3):330–336. doi: 10.1172/JCI105347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clegg J. B., Naughton M. A., Weatherball D. J. Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok). J Mol Biol. 1966 Aug;19(1):91–108. doi: 10.1016/s0022-2836(66)80052-9. [DOI] [PubMed] [Google Scholar]
  4. Clegg J. B., Weatherall D. J., Na-Nakorn S., Wasi P. Haemoglobin synthesis in beta-thalassaemia. Nature. 1968 Nov 16;220(5168):664–668. doi: 10.1038/220664a0. [DOI] [PubMed] [Google Scholar]
  5. Fuhr J., Natta C., Marks P. A., Bank A. Protein synthesis in cell-free systems from reticulocytes of thalassaemic patients. Nature. 1969 Dec 27;224(5226):1305–1307. doi: 10.1038/2241305a0. [DOI] [PubMed] [Google Scholar]
  6. Gilbert J. M., Anderson W. F. Cell-free hemoglobin synthesis. II. Characteristics of the transfer ribonucleic acid-dependent assay system. J Biol Chem. 1970 May 10;245(9):2342–2349. [PubMed] [Google Scholar]
  7. Heywood D., Karon M., Weissman S. Asymmetrical incorporation of amino acids in the alpha and beta chains of hemoglobin synthesized by thalassemic reticulocytes. J Lab Clin Med. 1965 Sep;66(3):476–482. [PubMed] [Google Scholar]
  8. Kan Y. W., Schwartz E., Nathan D. G. Globin chain synthesis in the alpha thalassemia syndromes. J Clin Invest. 1969 Nov;47(11):2512–2522. doi: 10.1172/JCI105933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Miller R. L., Schweet R. Isolation of a protein fraction from reticulocyte ribosomes required for de novo synthesis of hemoglobin. Arch Biochem Biophys. 1968 May;125(2):632–646. doi: 10.1016/0003-9861(68)90622-x. [DOI] [PubMed] [Google Scholar]
  10. Necheles T. F., Allen D. M., Gerald P. S. The many forms of thalassemia: definition and classification of the thalassemia syndromes. Ann N Y Acad Sci. 1969 Nov 20;165(1):5–12. doi: 10.1111/j.1749-6632.1969.tb27771.x. [DOI] [PubMed] [Google Scholar]
  11. Prichard P. M., Gilbert J. M., Shafritz D. A., Anderson W. F. Factors for the initiation of haemoglobin synthesis by rabbit reticulocyte ribosomes. Nature. 1970 May 9;226(5245):511–514. doi: 10.1038/226511a0. [DOI] [PubMed] [Google Scholar]
  12. Shafritz D. A., Anderson W. F. Factor dependent binding of methionyl-tRNAs to reticulocyte ribosomes. Nature. 1970 Aug 29;227(5261):918–920. doi: 10.1038/227918a0. [DOI] [PubMed] [Google Scholar]
  13. Shafritz D. A., Anderson W. F. Isolation and partial characterization of reticulocyte factors M1 and M2. J Biol Chem. 1970 Nov 10;245(21):5553–5559. [PubMed] [Google Scholar]
  14. Shafritz D. A., Prichard P. M., Gilbert J. M., Anderson W. F. Separation of two factors, M1 and M2, required for poly U dependent polypeptide synthesis by rabbit reticulocyte ribosomes at low magnesium ion concentration. Biochem Biophys Res Commun. 1970 Feb 20;38(4):721–727. doi: 10.1016/0006-291x(70)90641-8. [DOI] [PubMed] [Google Scholar]
  15. Weatherall D. J., Clegg J. B., Naughton M. A. Globin synthesis in thalassaemia: an in vitro study. Nature. 1965 Dec 11;208(5015):1061–1065. doi: 10.1038/2081061a0. [DOI] [PubMed] [Google Scholar]

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