By the late 1970s the physical structure of a gene was firmly established from work in bacteria. The sequences of the gene, the RNA, and the protein were colinearly organized and expressed. Since the science of genetics suggested that genes in eukaryotic organisms behaved similarly to those of prokaryotic organisms, it was naturally assumed that this bacterial gene structure was universal. It followed that if the gene structure was the same, then the mechanisms of regulation were probably very similar, and thus what was true of a bacterium would be true of an elephant.

However, many descriptive biochemical aspects of the genetic material and its expression in cells with nuclei suggested that the simple molecular biology of gene expression in bacteria might not be universal. First, obviously, RNAs transcribed from nuclear genes are physically separated from the translational machinery in the cytoplasm. Second, the DNA content of eukaryotic germ cells varied significantly among organisms without an apparent variation in the number of genes. Third, the previously described phenomenon of heterogeneous nuclear RNA (hnRNA) suggested that long RNAs were transcribed from diverse nuclear sequences (Damell, 1975). These hnRNAs had a short half-life relative to cytoplasmic mRNAs and thus could potentially be precursors to mRNAs (premRNAs). Furthermore, both the long hnRNA and the shorter mRNA appeared to have modified S’and 3’termini in common, a ‘mGpppX cap (Furuichi et al., 1975; Wei and Moss, 1974; Rottman et al., 1974) and polyadenylation tracts (Edmondset al., 1971; Leeet al., 1971; Darnellet al., 1971), respectively. The meaning of these observations concerning hnRNAs remained controversial as it was not possible to establish a precursor-product relationship between the nuclear RNA population and the cytoplasmic mRNA.