Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns

Journal Article · Tue Jun 30 04:00:00 EDT 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00387a004· OSTI ID:5998161

Loskutoff, D J; Linders, M; Keijer, J; Veerman, H; van Heerikhuizen, H; Pannekoek, H

Plasminogen activator inhibitor 1 (PAI-1) is the primary inhibitor of tissue-type plasminogen activator and thus performs an essential role in the regulation of the fibrinolytic process. It is a member of a large family of serine protease inhibitors (serpins). The authors determined the structure of the PAI-1 gene in order to more completely investigate the relationship of PAI-1 to other serpins and, at the same time, to begin to delineate structure-function relations in PAI-1 itself. A human genomic cosmid DNA library was screened and found to contain two independent clones, each harboring the entire PAI-1 gene. Restriction site mapping, electron microscopic inspection of heteroduplexes, and nucleotide sequence analysis all demonstrate that the PAI-1 gene is approximately 12.2 kilobase pairs in length and consists of nine exons and eight introns. All intron-exon boundaries are in accord with the GT-AG rule, including a cryptic acceptor splice site found in intron 7. The intron-exon pattern of the PAI-1 gene is distinct from that of most other serpins except that intron 3 of PAI-1 occupies an identical position as intron E of ovalbumin. Comparison of the authors data with the proposed subdomain structure of serpins suggests that seven of the eight introns may occupy a nonrandom position in the gene. These introns either delineate boundaries of individual structural subdomains or are located in random coil regions of the protein. Transcription of the PAI-1 gene in cultured vascular endothelial cells results in two distinct mRNA species. The data suggest that these two transcripts arise by alternative polyadenylation.

• Research Organization: Free Univ. of Amsterdam, Netherlands
• OSTI ID: 5998161
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:13; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOHYDRATES
CHEMICAL ACTIVATION
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DNA
DNA SEQUENCING
DRUGS
ENZYME INHIBITORS
FIBRINOLYSIS
FIBRINOLYTIC AGENTS
GENES
GLUCOPROTEINS
HEMATOLOGIC AGENTS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMINOGEN
PRIMATES
PROTEINS
PROTEOLYSIS
RADIOISOTOPES
RECOMBINANT DNA
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
TRANSCRIPTION
VERTEBRATES