The murine urokinase-type plasminogen activator gene

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The urokinase-type plasminogen activator (uPA) plays a crucial role in various physiological and pathological processes.
• Understanding the genetic regulation of uPA is essential for developing targeted therapies.

Purpose of the Study:

• To isolate and determine the nucleotide sequence of the murine uPA gene.
• To analyze the structural organization and regulatory elements of the murine uPA gene.
• To compare the murine uPA gene sequence with homologous genes in other species.

Main Methods:

• Isolation of the murine uPA gene from a BALB/c liver DNA cosmid library.
• Establishment of the complete nucleotide sequence of the gene.
• Bioinformatic analysis of gene structure, promoter elements, and regulatory sequences.
• Comparative sequence analysis with porcine and human uPA genes.

Main Results:

• The murine uPA gene comprises 11 exons within a 6710 bp region.
• Identified common RNA polymerase II promoter elements (TATA box, Sp1 site) near the transcription initiation site.
• Discovered a large polypurine tract upstream of the 5'-terminus with potential non-B-DNA conformation.
• Found a conserved dodecanucleotide sequence homologous to cAMP-modulated regulatory elements.
• Observed a high degree of evolutionary sequence conservation, including introns and flanking regions, compared to porcine and human uPA genes.

Conclusions:

• The murine uPA gene possesses conserved regulatory elements, including those responsive to cAMP.
• The extensive interspecies sequence conservation suggests critical functional importance of both coding and non-coding regions.
• This detailed characterization provides a foundation for further studies on uPA gene regulation and its role in biological systems.