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Three polyadenylated RNAs, 9, 7.3, and 3.5 kilobases long, of a human endogenous retrovirus, ERV3, are abundant in human placental chorion, representing about 0.03 to 0.05% of the total mRNA. We characterized the structure of these mRNAs by Northern blot and S1 nuclease mapping analyses. We found that all three RNAs were spliced mRNAs that lacked 5.9 kilobases of proviral sequence, including the gag gene and most of the pol gene. In contrast to the transcription pattern usual for other retroviruses, the transcription pattern of the ERV3 provirus did not include a genome-length mRNA. All three of the ERV3 mRNAs initiated transcription at the same point in the 5' long terminal repeat (LTR) and contained identical splice junctions in the provirus. The 3.5-kilobase RNA was a typical subgenomic proviral mRNA, with its polyadenylation site in the 3' LTR. The two larger ERV3 mRNAs, however, extended through the polyadenylation site in the 3' LTR and were spliced at a second position approximately 370 nucleotides downstream from the 3' LTR. This finding suggests that when the ERV3 retrovirus integrated at this genomic locus in an ancestor of humans, it integrated within or adjacent to a cellular gene.

The expression of viral oncogenes in cells transformed by acutely transforming retroviruses profoundly alters proliferation and differentiation in the target cell, suggesting that the cellular homologues of the viral oncogenes, the protooncogenes, have a role in normal cell proliferation and differentiation. To investigate the possible developmental role of protooncogenes in human embryogenesis, we have determined the spatial distribution of myc gene transcripts in early human embryos by using in situ hybridization of a labeled myc exon to thin sections. The results indicate a stage-and celltype-specific regulation of c-myc gene expression in primarily epithelial cells oflate frst trimester embryos. Furthermore, the data suggest that the linkage between c-myc gene expression and cellular proliferation holds for only a restricted set of embryonic cells.

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