Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during...

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The desmin gene (des) encodes a key intermediate filament protein crucial for muscle structure and function.
• Understanding the genetic organization and regulatory elements of the desmin gene is vital for insights into muscle development and disease.

Purpose of the Study:

• To isolate, characterize, and determine the complete nucleotide sequence of the human desmin gene (des).
• To compare the human des gene structure with that of the hamster des gene, focusing on exons, introns, and regulatory regions.
• To identify conserved regulatory elements in the 5'- and 3'-untranslated regions of the human des gene.

Main Methods:

• Recombinant DNA technology for gene isolation and cloning.
• DNA sequencing to determine the complete nucleotide sequence of the human desmin gene.
• Comparative sequence analysis between human and hamster desmin genes, including flanking regions and untranslated sequences.

Main Results:

• The 8.4-kb human desmin gene comprises nine exons and eight introns, with conserved exon positions and sequences compared to the hamster gene.
• Introns show sequence divergence but conserved splice junction signals; a 1.2-kb repetitive AluI family sequence was identified in human des gene introns.
• Conserved regulatory elements, including a 16-mer consensus element and an 11-bp sequence homologous to actin gene regulatory regions, were found in the 5'-flanking region.

Conclusions:

• The human desmin gene exhibits significant structural conservation with its hamster counterpart, particularly in exon organization.
• Conserved regulatory sequences in the flanking regions suggest shared transcriptional control mechanisms.
• A single 2.2 kb desmin RNA species is expressed in human striated and smooth muscle tissues.