Expression of the alpha-fetoprotein gene in adult rat liver

The adult rat liver contains three alpha-fetoprotein (AFP) mRNAs of 2.2 (minor), 1.7, and 1.5 kb. These transcripts share a common 3' sequence, but the 1.7- and 1.5-kb AFP mRNAs lack sequences present in the first seven 5' exons of the 2.2-kb AFP mRNA. S1 nuclease analysis maps the 1.7-kb mRNA at the 5' boundary of the eighth exon of the 2.2-kb AFP mRNA and the 1.5-kb mRNA in the middle of the eight exon. In a transformed fetal rat liver cell line, we have previously identified a 1.7-kb AFP mRNA which is encoded by an AFP cDNA (ARFP5) isolated from an adult rat liver cDNA library. The 90-bp 5' sequence of ARFP5, which is located in the seventh intron of the rat AFP gene, is not present in the 2.2-kb fetal AFP mRNA, although ARFP5 does contain nucleotide sequence present in the 2.2-kb AFP mRNA extending from the beginning of its eighth exon (nucleotide 873) to the 3' end. The 1.7-kb RNA in adult liver also hybridizes with the 90-bp 5' sequence of ARFP5, suggesting that the two 1.7-kb AFP mRNAs are similar. The developmental profile of these AFP transcripts shows that fetal rat liver contains mainly the 2.2-kb mRNA which decreases to a very low level around the fifth week after birth. The 1.7- and 1.5-kb AFP mRNAs can be visualized about the third and fourth weeks after birth, respectively, and are the major AFP mRNAs in the liver of rats that are older than 4 weeks. The levels of the AFP mRNAs in adult liver are approximately 0.4% of the AFP mRNA level in 18-day-old fetal liver. Both the 1.7- and 1.5-kb AFP mRNAs are actively translated; they direct the cell-free synthesis of two polypeptides of 50K and 44K. A 50K polypeptide is also the encoded product of the 1.7-kb mRNA in the transformed fetal rat liver cell line, suggesting that the 44K polypeptide may be encoded by the 1.5-kb AFP mRNA.