Abstract
Modified 5′-terminal structures (caps) of mRNA play an important role in the initiation of protein synthesis. A deficiency of 5′-capping and methylation has been suggested as a possible cause of β mRNA deficiency in β-thalassemia (β-thal). After incubating peripheral blood from β+-thal major, α-thal, nonthal adults with reticulocytosis, and erythroblastotic infants with [methyl-3H] methionine, the 5′-terminal structures of human α and β globin mRNA were labeled. To separate the 5′-terminal oligonucleotide of α mRNA from that of β mRNA, [3H]-labeled poly(A+) RNA was digested with RNase T1 and alkaline phosphatase, and the digest was fractionated by DFAE-Sephadex chromatography in 7 M urea. After sequence analysis, we found that the methylated 5′-termini of the α and β mRNAs are identical through the first three nucleotides: m7Gpppm6AmpCmp. Our data also indicate that addition of the four methyl groups to the 5′-end follows an orderly sequence. The rate of methylation of the 5′-terminus of β mRNA was compared to that of α mRNA in a patient with β+-thal major and in non-thal patients. No major differences in methylation were observed between the β+-thal and nonthal samples. We conclude that 5′-capping and methylation is not defective in our β+-thal patient.
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Cho, S., Cheng, TC., Fox, J. et al. 516 METHYLATED 5′-TFRMINI OF GLOBIN mRNAs IN SbT-THALASSEMIA. Pediatr Res 12 (Suppl 4), 449 (1978). https://doi.org/10.1203/00006450-197804001-00521
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DOI: https://doi.org/10.1203/00006450-197804001-00521