Human liver fibronectin complementary DNAs: identification of two different messenger RNAs possibly encoding the...

Human fibronectin polymorphism arises from variation in the C-terminal region [e.g., Sekiguchi, K., Siri, A., Zardi, L., & Hakomori, S. (1985) J. Biol. Chem. 260, 5105-5114]. In order to verify the chemical basis of the fibronectin polymorphism, cDNAs encoding the C-terminal region of human liver fibronectin have been isolated, sequenced, and compared with cDNAs encoding so-called "cellular fibronectin" (i.e., fibronectin produced by cultured cells in vitro). Among the five independent cDNAs thus isolated, two cDNAs, named pLF2 and pLF4, differed in the nucleotide sequence at the "type III connecting segment" (IIIcs) region. pLF4 contained 192 bases in this region whereas pLF2 completely lacked these bases. S1 mapping analysis indicated that both cDNAs with and without the 192 bases are faithful copies of two fibronectin mRNA species abundantly present in human liver. Comparison of the liver cDNAs with those coding for cellular fibronectin indicates that the latter cDNAs contain the 75-base and/or 93-base extra segments at the 5' and 3' boundaries of the 192-base IIIcs region. These extra segments have the consensus sequences for the 3' splice sites at their 3' ends, suggesting that fibronectin mRNAs with partial or complete deletion of the IIIcs sequence result from alternative splicing of a primary RNA transcript. Liver fibronectin cDNAs also lacked the 270-based "extra domain" (ED) segment present in some, but not all, cDNAs encoding cellular fibronectin. Thus, cellular fibronectin appears to have three extra peptide segments, encoded by the 75-base and 93-base segments in the IIIcs region and by the 270-base ED region, that are mostly absent in the liver fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)