Organization and expression of early genes of simian virus 40

Abstract

The early region of simian virus 40 codes for at least two immunologically related polypeptides: large-T and small-t, with apparent molecular weights of 90,000-100,000 and 15,000-20,000, respectively. Because small-t shares methionine-containing tryptic peptides with large-T, the two polypeptides are probably coded, in part, by a common nucleotide sequence. To locate the coding sequences for large-T and small-t in the DNA, the production of these proteins was examined after infection of CV-1 cells with wild-type and deletion mttants of simian virus 40. We found that a deletion at the distal portion of the early region alters the structure of large-T but not of small-t; but deletions within the region between map coordinates 0.59 and 0.55 result in an alteration or absence of small-t and a normal large-T. These findings have been rationalized by a model that proposes the existence of two early mRNAs, one coding for large-T and the other for small-t. Both mRNAs span virtually the entire early region; but the mRNA coding for large-T lacks the nucleotide sequence between map coordinates 0.59 and 0.54. We suggest that small-t is translated from the larger of the two mRNAs, beginning at or near its 5' end and terminating at a termination codon at about map coordinate 0.54. Large-T, on the other hand, is translated from the shorter mRNA, beginning at the same initiator codon, and, because of the deletion of the terminator codon at 0.54, translation proceeds to the terminator codon at or near map position 0.18.The genome of simian virus 40 (SV40) has a defined molecular structure and a small number of genes, each of which is expressed during a particular interval in its multiplication cycle. Its ability to cause tumors in vivo and transform cells in vitro provides an opportunity for analyzing the mechanism of these phenomena as well (see refs. 1 and 2 for a review of the molecular biology of SV40). The oncogenic event and maintenance of the transformed phenotype require the expression of one or more viral genes. Because only those viral functions that occur prior to the onset of viral DNA replication in the lytic cycle (the early functions) are expressed in transformed cells, this narrows the search for the putative oncogenes to the early genes. One of the viral coded products required for transformation is the T antigen or T polypeptide (large-T), a protein that is synthesized early in the lytic infection and is coded by the early region of the DNA (the A cistron); the same protein is made in SV40-transformed or tumor cells (1, 2).The T antigen has an apparent polypeptide molecular weight of 90,000-100,000 (3); consequently, almost the entire nucleotide sequence of the early region would be needed to code for its primary structure. Therefore, it was not anticipated that a set of mutants with deletions in the early region between map coordinates 0.59 and 0.54 would produce a normal T polypeptide (4). The interpretation offered at that time (4) suggested that the nucleotide sequence between map positions 0.59 and...

Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen

“…However, human cells expressing LT, hTERT and H-Ras cannot grow in an anchorage-independent manner or form tumors in animals without the additional introduction of ST (Hahn et al, 1999(Hahn et al, , 2002Yu et al, 2001). Several lines of evidence suggest that ST perturbs cellular targets that participate in human tumor development (Shenk et al, 1976;Crawford et al, 1978;Choi et al, 1988). The ability of ST to transform human cells requires binding to the abundant serine-threonine protein phosphatase 2A (PP2A) (Yang et al, 1991;Sontag et al, 1993).…”

Host nuclear proteins expressed in simian virus 40-transformed and -infected cells.

“…The second early antigen, small tumor antigen (t-Ag; apparent Mr, 20,000), is coded for by the region of SV40 DNA mapping from 0.67 to 0.54 map units. Viable deletion mutants mapping from 0.59 to 0.54 (6) have been shown to affect the size of t-Ag and to be defective in the transformation of certain cell types in culture (7,8); these deletion mutants are equivalent to the host-range mutants described by Benjamin (9) for polyoma.…”

Variable region genes for the immunoglobulin framework are assembled from small segments of DNA—A hypothesis

“…2). The light (5-7) and the heavy chains (8,9) (13) have now been found in a mouse f3-globin (14,15), rabbit globin (16), avian ovalbumin (17,18), viral proteins (19)(20)(21)(22)(23)(24)(25), some ribosomal DNA genes in Drosophila (26)(27)(28)(29), and tRNA genes in yeast (30).…”