The nucleotide sequence and genome organization of the polyoma early region: Extensive nucleotide and amino acid homology with SV40

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The nucleotide sequence of the early region of the polyoma genome has been determined by the chemical method of Maxam and Gilbert (1977) and the primed synthesis method of Sanger, Nicklen and Coulson (1978). The sequence consists of 3013 nucleotide pairs and contains the regions encoding the three related forms of the tumor antigens, as well as the regions encoding the origin of DNA replication and sequences regulating messenger RNA transcription and splicing. The extent of the open reading frames, together with estimated mRNA splice positions, defines potential coding regions and approximate sizes for the three forms of the tumor (T) antigens. There are uninterrupted open frames corresponding to the probable small t coding region, the 5′ ends of the large T and medium T coding regions, the maximum length for the 3′ end of the large T coding region, and a region potentially available for the 3′ end of the medium T antigen. The 5′ untranslated region contains sequences that are capable of interacting in several different ways with the 3′ end of the 18S ribosomal RNA, thereby representing a possible ribosomal binding site. There are two other 5′ untranslated sequences similar to sequences found at the 5′ ends of other eucaryotic genes that might represent capping signals and/or promoter signals. The 3′ untranslated region contains the sequence 5′-AA-TAAA-3′ just 3′ to the TGA termination triplet, a sequence that may constitute an eucaryotic polyadenylation signal. Codon utilization in the polyoma early region shows deviation from random, especially in its deficiency of triplets ending in TC and in its paucity of CG. There is extensive nucleotide, and deduced amino acid, homology with the early region of SV40 ( Fiers et al., 1978; Reddy et al., 1978) throughout regions thought to encode the respective small t and large T antigens. Furthermore, a portion of the possible medium T antigen coding region shows homology with the 3′ end of the SV40 large T antigen coding region, suggesting that the function of the polyoma medium T antigen is performed by the SV40 large T antigen.