Alternative exon splicing within the amino-terminal nontriple-helical domain of the rat pro-α1(XI) collagen chain generates multiple forms of the mRNA transcript which exhibit tissue-dependent variation

Type XI collagen is an integral, although minor component of cartilage collagen fibrils. We have established that alternative exon usage is a mechanism for increasing structural diversity within the amino-terminal non-triple helical domain of the pro-α1(XI) collagen gene. cDNA clones spanning the amino-terminal domain were selected from a rat chondrosarcoma library, and were shown to contain two major sequence differences from the previously reported human sequence. The first difference was the replacement of sequence encoding an acidic domain of 39 amino acids in length by a sequence encoding a 51-amino acid basic domain with a predicted pi of 11.9. The second difference was the absence of a sequence that would translate into a highly acidic 85-amino acid sequence downstream from the first variation. These two changes, expressed together, result in the replacement of most of the acidic domain with one that is smaller and basic. These two sequence differences serve to identify subdomains of a variable region, designated V1 and V2, respectively. V1a is defined as the acidic 39-amino acid sequence element and V1b is defined as the 51-amino acid basic sequence. Analysis of genomic DNA revealed that both V1a and V1b are encoded by separate adjacent exons in the rat genome and V2 is also encoded in a single exon downstream. Analysis of mRNA from cartilage-derived sources revealed a complex pattern of α1-(XI) transcript expression due to differential exon usage. In non-cartilage sources, the pattern is less complex; the most prevalent form is the one containing the two acidic sequences, V1a and V2.