Transcriptional deviation of the rat insulin-like growth factor II gene initiated at three alternative leader-exons between neonatal tissues and ascites hepatomas

Abstract Insulin-like growth factor II (IGFII) is a mitogenic polypeptide, the mRNAs of which are present in multiple forms, despite derivation from a single gene. In the present study, we observed nearly full-length rat IGFII mRNA structures of major species with three alternative 5′-untranslated sequences and a common unusually-long 3′-untranslated region. These three 5′ sequences (E1, E2 and E3) locate at different sites on the rat IGFII genome and are therefore independent leader-exons. Northern blotting using probes specific to E1, E2 and E3 sequences revealed major bands at 3.8 kilobases (kb), 4.6 kb and 3.6 kb in nucleotide length, respectively. The E1, E2 and E3 promoters were functional in all rat neonatal tissues examined and in the adult brain, and the relative level of mRNA species was fairly constant, although the bulk expression varied from tissue to tissue. Thus, the three mRNAs initiated from the single rat IGFII gene are co-ordinately regulated. However, this relative transcriptional constancy deviated variously in several lines of transplantable rat ascites hepatomas, thereby indicating that each mRNA level can also be regulated independently.