Human genes for complement components C1r and C1s in a close tail-to-tail arrangement

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• Complement component C1s (C1s) is a crucial part of the classical complement pathway.
• Understanding the genetic organization and expression of C1s is vital for comprehending immune responses.

Purpose of the Study:

• To isolate and characterize complementary DNA (cDNA) clones for human C1s.
• To determine the nucleotide sequence and analyze the genetic structure of human C1s.
• To investigate the genomic organization and tissue-specific expression of C1r and C1s genes.

Main Methods:

• cDNA library construction from human liver and HepG2 cell poly(A)+ RNAs.
• Nucleotide sequencing of the largest cDNA insert (2664 bp).
• DNA blotting and sequencing for genomic analysis.
• RNA blot analysis for gene expression studies.

Main Results:

• A 2664 bp cDNA clone for human C1s was sequenced, revealing its complete nucleotide sequence including untranslated regions, signal peptide, and zymogen coding sequence.
• The amino acid sequence of C1s showed 40.5% identity to C1r, preserving domain structure.
• Human C1r and C1s genes are located approximately 9.5 kilobases apart in a "tail-to-tail" arrangement.
• Both C1r and C1s genes are predominantly expressed in the liver, with significantly lower expression in other tissues.
• Multiple mRNA sizes for C1r and C1s suggest alternative RNA processing, potentially alternative polyadenylylation.

Conclusions:

• The study provides a detailed characterization of the human C1s cDNA and its genetic organization.
• The close proximity and coordinated expression of C1r and C1s genes in the liver suggest a functional relationship.
• Alternative RNA processing mechanisms may contribute to the regulation of C1r and C1s gene expression.