Genetic structure and transforming sequence of avian sarcoma virus UR2

Abstract

We have recently shown that a newly isolated avian sarcoma virus, UR2, is defective in replication and contains no sequences homologous to the src gene of Rous sarcoma virus. In this study, we analyzed the genetic structure and transforming sequence of UR2 by oligonucleotide fingerprinting. The sizes of the genomic RNAs of UR2 and its associated helper virus, UR2AV, were determined to be 24S and 35S, respectively, by sucrose gradient sedimentation. The molecular weight of the 24S UR2 genomic RNA was estimated to be 1.1 x 106, corresponding to 3,300 nucleotides, by gel electrophoresis under the native and denatured conditions. RNase T1 oligonucleotide mapping indicated that UR2 RNA contains seven unique oligonucleotides in the middle of the genome and shares eight 5'-and six 3'-terminal oligonucleotides with UR2AV RNA. From these data, we estimated that UR2 RNA contains a unique sequence of about 1.2 kilobases in the middle of the genome, and contains 1.4 and 0.7 kilobases of sequences shared with UR2AV RNA at the 5' and 3' ends, respectively. Partial sequence analysis of the UR2-specific oligonucleotides by RNase A digestion revealed that there are no homologous counterparts to these oligonucleotides in the RNAs of other avian sarcoma and acute leukemia viruses studied to date. UR2-transformed non-virus-producing cells contain a single 24S viral RNA which is most likely the message coding for the transforming protein of UR2. On the basis of the uniqueness of the transforming sequence, we concluded that UR2 is a new member of the defective avian sarcoma viruses.

Cellular Sequences Related to Three New onc Genes of Avian Sarcoma Virus ( fps, yes , and ros ) and Their Expression in Normal and Transformed Cells

“…In the first part of this study, we demonstrated that the unique sequence of UR2, denoted ros, is nonhomologous to src, fps, or yes sequences and thus apparently represents a new onc gene of ASV. This is consistent with our previous results obtained from fingerprinting analyses of viral RNAs (55). It is of interest to note that all of the gene products of these four onc sequences have been reported to be associated with protein kinase activity specific for phosphorylation of tyrosine residues on substrate proteins (13,14,30,38,41,54).…”

“…The functional src message (21S RNA) has been estimated to be about one-fifth to one-fourth of total viral RNA (24). On the other hand, genomic RNAs of defective ASVs represent the only viral transcripts in transformed cells (54,55;Shibuya,unpublished data), and they are known to serve as messages for transforming proteins (14).…”

“…By comparison of tryptic peptides of transforming proteins, Esh sarcoma virus was shown to be related to Y73 in the unique sequences (19). On the other hand, the unique sequence of UR2 (ros) has been suggested to be different from other onc genes of ASV and of representative avian acute leukemia viruses (55).…”

“…These viruses appear to be different from RSV but similar to one another in several characteristics. First, they are all defective in virus replication, because their viral genomes contain unique sequences unrelated to avian C-type retroviruses, in place of sequences required for virus replication (19,23,31,37,54,55,60). Second, their genomes encode unique proteins ranging from 68,000 to 140,000 daltons which are precipitable by antisera against viral structural proteins coded by the gag gene of avian retroviruses.…”

Established, emerging and elusive molecular targets in the treatment of lung cancer

“…TP53, KRAS, and MYC) molecular targets in the treatment of lung cancer. We synthesize a large and rapidly growing body of literature regarding the discovery and therapeutic inhibition of these targets in lung cancer.Similarly to ALK, ROS1 encodes an orphan (no identified ligand) membrane-bound RTK [85,86]. Also similarly to ALK, chromosomal rearrangements involving ROS1 have been identified in ∼1% of lung adenocarcinomas [87].…”