Alternative splicing of the NC1 domain of the human alpha 3(IV) collagen gene. Differential expression of mRNA transcripts that predict three protein variants with distinct carboxyl regions.

Three clones of NC1 of alpha 3(IV) collagen, named Q1, L5, and V, were isolated from human kidney; these predict three variant alpha 3(IV) NC1 domains of 232-, 60-, and 199-amino acid residues, respectively, with unique COOH-termini. The human collagen IV gene (COL4A3) was isolated and characterized, and it was shown that the cDNA variants arose from alternative splicing by deletion of exon 4 in L5 and deletion of exon 2 in V. The mRNA transcripts were differentially expressed in fetal and adult human kidney with Q1 the major species. Exon 4-L5 lacked 183 residues from the carboxyl terminus with a frameshift producing a unique 11-amino acid terminal peptide. In exon 2-V a frameshift resulted in a unique V carboxyl terminus of 53 novel peptides with a new glycosylation site. The size of recombinant proteins indicated the frameshifts and new stop codons were as predicted. The multiple forms of the alpha 3(IV) NC1 region may contribute to autoimmune glomerular disease and hereditary nephritis, in which this portion of the collagen IV molecule is thought to play an important role.