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

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.3.1041· OSTI ID:7068675

Vidaud, M; Vidaud, D; Amselem, S; Rosa, J; Goossens, M ^[1]; Gattoni, R; Stevenin, J ^[2]; Chibani, J ^[3]

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1. Institut National de la Sante et de la Recherche Medicale, Creteil (France)
2. Institut National de la Sante et de lay Recherche Medicale, Strasbourg (France)
3. 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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:3; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANEMIAS
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CLONING
CYTOSINE
DAYS LIVING RADIOISOTOPES
DISEASES
DNA BASE TRANSITIONS
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ERYTHROCYTES
GENES
GLOBIN
GUANINE
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
HYBRIDIZATION
HYDROXY COMPOUNDS
INHIBITION
ISOTOPES
LIGHT NUCLEI
MATERIALS
MESSENGER-RNA
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PURINES
PYRIMIDINES
RADIOISOTOPES
RNA
STRUCTURAL CHEMICAL ANALYSIS
SYMPTOMS
TRANSCRIPTION