Regulation of SV40 gene expression through RNA splicing.
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Antigens, Neoplasm↗
Biomedical subjects
I Seif
Publications and source records attributed to I Seif.
BKV splice sequences based on analysis of preferred donor and acceptor sites.
We have determined the DNA sequences which correspond to the splicing regions in the transcripts of human papovavirus BKV, an evolutionary variant of SV40. To precisely localize the excision points in the BKV sequence, we have conducted a preliminary analysis of numerous viral and eukaryotic splice site sequences. This analysis suggests that the preferred sequence for the donor site belongs to at least one of four groups: Pu↓GTAxG, Pu↓GTAxxT, Pu↓GTxxGT, Pu↓GTxAG (↓ = the cleavage site). These four groups derive from the two basic sequences, Pu↓GTxxG and Pu↓GTA. An optimal donor site might be: AG↓GTAAGT. The preferred sequence for the acceptor site is of the form PyPyxPyAG↓; no dinucleotide AG occurs within 13 nucleotides prior to the terminal AG of the 3' end of the intervening sequences. As we have found in this study of BKV splice sites, the sequences for the preferred donor and acceptor sites provide predictive value in localizing RNA splice points when the DNA sequence is known.
BK Virus↗
The genome of human papovavirus BKV.
The complete DNA sequence of human papovavirus BKV(Dun), consisting of 5153 nucleotide pairs, is presented. We describe the segments of the genome which correspond to the replication origin, the tandem repeated sequences, the 5' and 3' ends of the mRNAs, the splice sites, the early and late viral proteins and the putative viral polypeptides. These BKV DNA sequences are compared with analogous regions in the SV40 and Py virus genomes in an attempt to localize viral functions for lytic growth and transformation.
Amino Acid Sequence↗
Nucleotide sequence of the BK virus DNA segment encoding small t antigen.
The nucleotide sequence from 0.64 to 0.53 map units in the BK virus genome coding for the small t protein has been determined. There is only one open reading frame that can code for a polypeptide of 172 amino acids, the putative small t protein. Beyond this segment, multiple termination codons are present in all three reading frames. There is considerable nucleotide and amino acid sequence homology between this region of BK virus and the analogous region of simian virus 40, especially in the proximal portion from 0.64 to 0.60 map units which is most likely common to the small t and large T BK virus proteins. A comparison of the conserved sequences within the early papovavirus genes both confirms the evolutionary relationship between these viruses and suggests the amino acid composition of the regions required for T antigen functions.
Antigens, Neoplasm↗
Behavioral characteristics of mice with genetic knockout of monoamine oxidase type A.
Transgenic mice of line Tg8 were used to study the effects of deletion of the monoamine oxidase type A gene and the absence of the corresponding enzyme on behavior. These experiments showed that Tg8 mice with genetic knockout of monoamine oxidase type A differed from mice of the parental line C3H/HeJ by lower levels of the startle reflex in response to an acoustic signal, while there was no difference in the prestimulus inhibition of the startle response. Tg8 mice showed decreased investigative activity and decreases in the number of sector crossings in the light-dark anxiety test. There were significant increases in aggression as a motivation in male Tg8 mice, which was manifest as an increase in the number of mice demonstrating aggression and a decrease in the latent period of attack. The intensity of aggression changed to a lesser extent - the number of fights even decreased, though longer periods of keeping mice together resulted in increased numbers of deaths among intruder mice. At the same time, there were no significant differences between mice with genetic knockout of monoamine oxidase type A and control mice in terms of the expression of sexual activation: the behavioral responses of Tg8 males to presentation of females was marked and was no different from that of male C3H/HeJ mice. Knockout of the gene had no effect on movement activity on behavior in an elevated cross-shaped maze or in the test for predisposition to catalepsy.
Aggression↗
A common function for polyoma virus large-T and papillomavirus E1 proteins?
Nucleotide sequencing has revealed a common genetic organization for three papillomaviruses: BPV-1 (bovine papillomavirus type 1), HPV-1 (human papillomavirus type 1a) and HPV-6 (human papillomavirus type 6b). Several open reading frames, corresponding to as yet uncharacterized proteins, were observed in these genomes in the region that is required for oncogenic transformation by BPV-1 and for plasmidial maintenance of its genome. The longest of these frames, E1, is also the most conserved between the three viruses; we have compared the amino acid sequence of its putative product ('E1 protein') with those of the large-T proteins of three polyoma viruses and report here significant homologies in their carboxy-terminal halves, extending for over 200 amino acids. Moreover, similar secondary structures were predicted in this region, especially in two blocks of homologous residues, which correspond in the large-T proteins of polyoma and simian virus 40 (SV40) viruses to sites involved in the ATPase and nucleotide-binding activities. These observations suggest that the papillomavirus E1 proteins might have a function in common with the polyoma virus large-T proteins (which are required for the initiation of viral DNA replication). As it was suggested recently that the E1 gene product is involved in maintaining the BPV-1 genome as a plasmid in transformed cells, we speculate that the structural features conserved in these otherwise very different viruses are general characteristics of eukaryotic proteins involved in the control of DNA replication.
Amino Acid Sequence↗
[Characteristics of behavior of knockout mice with genetic monoamine oxidase A deficiency].
The effect of deletion of monoamine oxidase A (MAO A) in the gene encoding on behavior of transgenic Tg8 mice was studied. A decrease in the amplitude of acoustic startle reflex rather than the prepulse inhibition was found in lacking MAO A Tg8 mice, as compared with the control C3H strain. The exploratory activity in the hole-board test in Tg8 was decreased as well as the number of crossed lines in the light-dark test. Tg8 mice showed decreased latency and increased intensity of intermale aggression. At the same time, no difference was found between Tg8 and C3H mice in locomotor activity, in the expression of sexual motivation, and in the behavior in the elevated plus-maze test. No predisposition to catalepsy was shown.
Acoustic Stimulation↗