Abstract
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.
Keywords: reticulocytes, polyribosomes, alpha chains, beta chains
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- 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]
- 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]
- Gabuzda T. G., Nathan D. G., Gardner F. H. THE TURNOVER OF HEMOGLOBINS A, F, AND A(2) IN THE PERIPHERAL BLOOD OF THREE PATIENTS WITH THALASSEMIA. J Clin Invest. 1963 Nov;42(11):1678–1688. doi: 10.1172/JCI104854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunt R. T., Hunter A. R., Munro A. J. Control of haemoglobin synthesis: a difference in the size of the polysomes making alpha and beta chains. Nature. 1968 Nov 2;220(5166):481–483. doi: 10.1038/220481a0. [DOI] [PubMed] [Google Scholar]
- Hunt T., Hunter T., Munro A. Control of haemoglobin synthesis: distribution of ribosomes on the messenger RNA for alpha and beta chains. J Mol Biol. 1968 Aug 28;36(1):31–45. doi: 10.1016/0022-2836(68)90217-9. [DOI] [PubMed] [Google Scholar]
- Hunt T., Hunter T., Munro A. Control of haemoglobin synthesis: rate of translation of the messenger RNA for the alpha and beta chains. J Mol Biol. 1969 Jul 14;43(1):123–133. doi: 10.1016/0022-2836(69)90083-7. [DOI] [PubMed] [Google Scholar]
- INGRAM V. M., STRETTON A. O. Genetic basis of the thalassaemia diseases. Nature. 1959 Dec 19;184:1903–1909. doi: 10.1038/1841903a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Kazazian H. H., Jr, Freedman M. L. The characterization of separated alpha and beta-chain polyribosomes in rabbit reticulocytes. J Biol Chem. 1968 Dec 25;243(24):6446–6450. [PubMed] [Google Scholar]
- Lodish H. G., Housman D., Jacobsen M. Initiation of hemoglobin synthesis. Specific inhibition by antibiotics and bacteriophage ribonucleic acid. Biochemistry. 1971 Jun 8;10(12):2348–2356. doi: 10.1021/bi00788a027. [DOI] [PubMed] [Google Scholar]
- Nathan D. G., Gunn R. B. Thalassemia: the consequences of unbalanced hemoglobin synthesis. Am J Med. 1966 Nov;41(5):815–830. doi: 10.1016/0002-9343(66)90039-8. [DOI] [PubMed] [Google Scholar]
- Nienhuis A. W., Laycock D. G., Anderson W. F. Translation of rabbit haemoglobin messenger RNA by thalassaemic and non-thalassaemic ribosomes. Nat New Biol. 1971 Jun 16;231(24):205–208. doi: 10.1038/newbio231205a0. [DOI] [PubMed] [Google Scholar]