Abstract
We have studied mechanisms causing reduced g mRNA accumulation in β-thal. One patient was studied by recombinant DNA cloning, nucleotide sequencing and in vitro functional analysis of the β-thal gene, and five others, by analysis of newly synthesized mRNA after pulse-chase labeling of erythroblasts with 3H-uridine. The cloned β-thal gene exhibited normal transcription in a cell-free system. The only nucleotide sequence abnormality occurs within the small intervening sequence (intron) and creates a potential anomalous splicing site in the mRNA precursor, suggesting a structural basis for defective processing. In four additional patients, defective β mRNA processing was also observed. The initial β/α 3H mRNA ratios of pulse-labeled RNA were normal, indicating normal transcription, but abnormally high accumulation of unprocessed β mRNA precursur sequences (introns) occurred in each case. A fifth patient exhibited normal 3H β mRNA synthesis and processing in nuclear RNA, but β mRNA in cytoplasm declined to steady-state levels during a 20-hour “chase,” indicating cytoplasmic instability. These studies identify at least two distinct post-transcriptional lesions in β mRNA metabolism in β-thal: inefficient processing of introns and cytoplasmic instability of mature β mRNA.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Benz, E., Spritz, R., Scarpa, A. et al. 789 ABNORMAL METABOLISM OF β mRNA IN β+-THALASSEMIA (β-THAL). Pediatr Res 15 (Suppl 4), 574 (1981). https://doi.org/10.1203/00006450-198104001-00813
Issue Date:
DOI: https://doi.org/10.1203/00006450-198104001-00813