Human fibronectin: cell specific alternative mRNA splicing generates polypeptide chains differing in the number of internal repeats.

The nucleotide sequence of five independent cDNA clones, which cover 4843 nucleotides from the poly(A) addition site of human fibronectin (FN) mRNA was determined. The deduced amino acid sequence (1383 residues) covers the COOH-terminal 60% of human FN, spanning the C-terminus, fibrin-, heparin- and cell-binding domains, and shows the exact location of the only two free sulphydryl groups present in each subunit chain. We have recently reported two different FN mRNA species; one of them containing an additional 270 nucleotide insert (ED) that encodes exactly one of the homology type III repeats of the protein. The two mRNAs arise by alternative splicing of a common precursor. S1 nuclease mapping of cDNA/RNA hybrids shows that the expression of the two mRNAs is cell specific. Liver only produces the mRNA without the ED, whereas hepatoma cells, breast tumor cells and normal fibroblasts produce both forms of mRNA. Another area of alternative splicing generating three different FN mRNAs in rat liver has been reported by Schwarzbauer et al (16). We here provide evidence for the existence in human cells of a fourth mRNA species different from the three described in rat liver.