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Posttranscriptional defects in beta-globin messenger RNA metabolism in beta-thalassemia: abnormal accumulation of beta-messenger RNA precursor sequences
- Source :
- Journal of Clinical Investigation. 68:1529-1538
- Publication Year :
- 1981
- Publisher :
- American Society for Clinical Investigation, 1981.
-
Abstract
- The production of beta-globin messenger RNA (mRNA) in beta-thalassemic erythroblasts was studied during pulse-chase incubations with [3H]uridine. Globin [3H]mRNA was quantitated by molecular hybridization to recombinant DNA probes complementary to globin mRNA and mRNA precursor sequences. Each of six patients with beta +-thalassemia produced normal amounts of globin alpha and beta [3H]mRNA during a 20-min pulse incubation, but the beta/alpha [3H]mRNA ratio declined to steady-state levels during a chase incubation, suggesting posttranscriptional defects in beta-globin mRNA metabolism. beta-globin mRNA precursor production was estimated by measurement of [3H]RNA sequences hybridizing to a pure DNA probe containing only the large intervening sequence (intron) of the beta-mRNA precursor. Four of the patients exhibited abnormal accumulation of 3H-beta-intron sequences (2-10 times normal), indicating abnormal posttranscriptional processing. In the remaining two patients, one of whom is known to carry a mutation in the small intron of the beta-globin gene, accumulation of large 3H beta-intron RNA and beta-globin [3H]mRNA was normal in nuclei, but the ratio of beta/alpha [3H]mRNA in cytoplasm was reduced, suggesting a different posttranscriptional defect in beta-mRNA processing. These findings imply the existence of heterogeneous posttranscriptional abnormalities in beta-globin mRNA metabolism in different patients with beta-thalassemia. The initial rates of gamma- and delta-mRNA synthesis were low in all patients, suggesting that the low level of expression of these genes in adults is mediated at the transcriptional level.
- Subjects :
- Adult
Cytoplasm
Erythrocytes
Adolescent
Transcription, Genetic
Biology
hemic and lymphatic diseases
P-bodies
medicine
Humans
RNA, Messenger
Globin
Child
Gene
Cell Nucleus
Messenger RNA
Base Sequence
Intron
Nucleic Acid Hybridization
Nucleic Acid Precursors
RNA
General Medicine
Molecular biology
Globins
Cell nucleus
Phenotype
medicine.anatomical_structure
Thalassemia
Precursor mRNA
Plasmids
Research Article
Subjects
Details
- ISSN :
- 00219738
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....e11368f7afd3830ac0a61e3cb9cbbd9f