Hemoglobin messenger RNA

Hemoglobin messenger RNA from human bone marrow. J. Clin. Invest. 1973, 52, 1735-1745. 

Messenger RNA combines with ribosomes to form polysomes containing several ribosome units, usually 5 (e.g., during hemoglobin synthesis), complexed to the messenger RNA molecule. This aggregate structure is the active template for protein biosynthesis. 

The total number of proteins found in nature is extremely large. The 1992 edition of the Enzyme List (Webb, 1992) lists 3196 enzymes. The total number of proteins in a eukaryotic cell has been estimated to be between 10,000 and 20,000 (Alberts et al., 1989), based upon the number of different messenger RNAs in a typical eukaryotic cell. This number does not reflect the thousands of natural mutants of any one protein that may occur. (Approximately 500 naturally occurring mutants of human hemoglobin have been identified to date.) Nor does it take into account the fact that there are often very substantial differences in homologous proteins that perform the same function in different species. A minimal estimate of the number of different proteins in living systems on earth would be on the order of 10,000 x 500 X the number of species i.e., literally, billions. 

Most of the 9 S RNA which is synthesized after addition of erythropoietin is likely to be the hemoglobin messenger, but some histone messenger may also be present in this fraction (Jacobs-Lorena et ah, 1972). It has not yet been shown that erythropoietin induced 9 S RNA can serve as a globin messenger. But 9 S globin messenger from other sources has been faithfully translated in cell-free systems or after injection into Xenopus oocytes (Lebleu et ah, 1971 Lane et ah, 1971). 

Hunt and Laycock [192] have separated two different messenger RNA s from hemoglobin—one sedimenting at 10 S, the other sedimenting at 8 S. The reason for the existence of two messengers in reticulocytes is still not clear. 

Hunt, J.A., Laycock, D.G. Characterization of messenger RNA for hemoglobin. Cold Spr. Harb. Symp. quant. Biol. 34, 579-584 (1969)... 

Kaempfer, R., and Kaufman, J., 1972, Translational control of hemoglobin synthesis by an initiation factor required for recycling of ribosomes and for their binding to messenger RNA, Proc. Natl. Acad. Sci. USA 69 3317. 

Differentiation of cells of the erythroid series is controlled by the hormone erythropoietin. Anemia stimulates erythropoietin formation, and this stimulates erythropoiesis. Erythropoietin also increases hemoglobin synthesis by stimulating synthesis of the corresponding messenger RNA (Krantz and Goldwasser, 1965). However, the possible link between erythropoietin and activation of adult hemoglobin (HbA and not HbF) has not yet been studied. 

A long-tailed messenger. Another thalassemic patient had a mutation leading to the production of an mRNA for the (3 chain of hemoglobin that was 900 nucleotides longer than the normal one. The poly(A) tail of this mutant mRN.A was located a few nucleotides after the only AAUAA.A sequence in the additional sequence. Propose a mutation that would lead to the production of this altered in RNA. 

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