Differential expression of a cysteine-rich domain in the amino-terminal propeptide of type II (cartilage) procollagen by alternative splicing of mRNA

M. C. Ryan, L. J. Sandell

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Abstract

Type II collagen, like other fibrillar collagens, is synthesized as a procollagen containing amino (NH2)- and carboxyl (COOH)-terminal extension peptides. Based on cDNA cloning of human (Baldwin, C.T., Reginato, A.M., Smith, C., Jimenez, S.A., and Prockop, D.J. (1989) Biochem. J. 262, 521-528) and rat (Kohno, K., Martin, G.R., and Yamada, Y. (1984) J. Biol. Chem. 259, 13668-13673) type II procollagen, it was concluded that much of the NH2-terminal propeptide seen in pro-α1(I) was missing. Analysis of human genomic clones for type II collagen revealed an additional exon encoding a 69-amino acid cysteine-rich domain in the NH2-terminal propeptide. This exon (exon 2) is expressed in the mRNA population of chondrocytes isolated from human fetal skeleton and notochord, juvenile costal cartilage, and bovine articular cartilage. Oligonucleotide probes spanning specific exon boundaries were used to detect two populations of procollagen mRNA by Northern blot analysis. Amplification of cDNA templates using polymerase chain reaction provided direct evidence for two distinct pro-α1(II) collagen mRNAs. DNA sequence analysis showed that the two mRNAs resulted from the alternative splicing of exon 2. The protein domain encoded by exon 2 is conserved between the fibrillar collagens and two other extracellular matrix proteins, thrombospondin and von Willebrand factor. In fibrillar collagens, this protein domain may play a regulatory role in fibrillogenesis and feedback inhibition of collagen biosynthesis. Consequently, the differential expression of this protein domain could alter the biosynthesis or fibril formation of type II collagen. In addition, the expression of exon 2 may be a marker for a distinct population of chondrocytes.

Original languageEnglish
Pages (from-to)10334-10339
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number18
StatePublished - Jul 24 1990

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