A five prime splice-region G yields C mutation in exon 1 of the human. beta. -globin gene inhibits pre-mRNA splicing: A mechanism for. beta. sup + -thalassemia
- Institut National de la Sante et de la Recherche Medicale, Creteil (France)
- Institut National de la Sante et de lay Recherche Medicale, Strasbourg (France)
- Faculte de Pharmacie, Monastir (Tunisia)
The authors have characterized a Mediterranean {beta}-thalassemia allele containing a sequence change at codon 30 that alters both {beta}-globin pre-mRNA splicing and the structure of the homoglobin product. Presumably, this G {yields} C transversion at position {minus}1 of intron 1 reduces severely the utilization of the normal 5{prime} splice site since the level of the Arg {yields} Thr mutant hemoglobin (designated hemoglobin Kairouan) found in the erythrocytes of the patient is very low (2% of total hemoglobin). Since no natural mutations of the guanine located at position {minus}1 of the CAG/GTAAGT consensus sequence had been isolated previously. They investigated the role of this nucleotide in the constitution of an active 5{prime} splice site by studying the splicing of the pre-mRNA in cell-free extracts. They demonstrate that correct splicing of the mutant pre-mRNA is 98% inhibited. Their results provide further insights into the mechanisms of pre-mRNA maturation by revealing that the last residue of the exon plays a role at least equivalent to that of the intron residue at position +5.
- OSTI ID:
- 7068675
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:3; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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DNA BASE TRANSITIONS
MESSENGER-RNA
MUTATIONS
ANEMIAS
CYTOSINE
DNA SEQUENCING
DNA-CLONING
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GUANINE
INHIBITION
PATIENTS
PHOSPHORUS 32
TRANSCRIPTION
AMINES
AROMATICS
AZAARENES
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BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
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BLOOD CELLS
BODY FLUIDS
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DNA HYBRIDIZATION
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
HYBRIDIZATION
HYDROXY COMPOUNDS
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NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHOSPHORUS ISOTOPES
PURINES
PYRIMIDINES
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550201* - Biochemistry- Tracer Techniques