共查询到20条相似文献,搜索用时 31 毫秒
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Chromosomal position effects determine transcriptional potential of integrated mammary tumor virus DNA 总被引:32,自引:0,他引:32
We have investigated two mammary tumor virus proviruses that are integrated at different chromosomal sites in the genomes of two clonal isolates of cultured rat hepatoma cells. One of these cell lines, J2.17, expresses MTV2 RNA only in the presence of glucocorticoid hormones. In contrast, the proviral genes in the other line, J2.15, fail to be transcribed in the presence or absence of glucocorticoids, despite the fact that the viral genes and the cellular components that mediate hormone responses appear intact and normal. Low-level DNAase I digestion of chromosomes in isolated nuclei reveals that the J2.17 MTV DNA sequences are packaged in chromatin that is highly sensitive to DNAase I attack, whereas the chromatin of the J2.15 provirus is relatively resistant to DNAase I. These results demonstrate that the same genetic element located at two different chromosomal loci within a single cell line can differ in both chromatin structure and gene expression. Analysis of the chromatin structure of the appropriate DNA sequences in uninfected HTC cells suggests that the difference in the chromatin structure of the two proviruses may reflect a “spreading effect”, in which heterologous integrating DNA is packaged into chromatin that is similar in configuration to the surrounding chromatin. Thus, we propose that chromosomal position determines the folding pattern of the newly introduced DNA sequences, and that this pattern in turn determines whether the genes can subsequently be expressed in response to the hormonal inducing signal. 相似文献
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Efficient polyadenylation of Rous sarcoma virus RNA requires the negative regulator of splicing element 总被引:5,自引:2,他引:3
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Rous sarcoma virus pre-mRNA contains an element known as the negative regulator of splicing (NRS) that acts to inhibit viral RNA splicing. The NRS binds serine/arginine-rich (SR) proteins, hnRNP H and the U1/U11 snRNPs, and appears to inhibit splicing by acting as a decoy 5′ splice site. Deletions within the gag gene that encompass the NRS also lead to increased read-through past the viral polyadenylation site, suggesting a role for the NRS in promoting polyadenylation. Using NRS-specific deletions and mutations, we show here that a polyadenylation stimulatory activity maps directly to the NRS and is most likely dependent upon SR proteins and U1 and/or U11 snRNP. hnRNP H does not appear to mediate splicing control or stimulate RSV polyadenylation, since viral RNAs containing hnRNP H-specific mutations were spliced and polyadenylated normally. However, the ability of hnRNP H mutations to suppress the read-through caused by an SR protein mutation suggests the potential for hnRNP H to antagonize polyadenylation. Interestingly, disruption of splicing control closely correlated with increased read-through, indicating that a functional NRS is necessary for efficient RSV polyadenylation rather than binding of an individual factor. We propose a model in which the NRS serves to enhance polyadenylation of RSV unspliced RNA in a process analogous to the stimulation of cellular pre-mRNA polyadenylation by splicing complexes. 相似文献
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G L Firestone 《The Journal of biological chemistry》1983,258(10):6155-6161
The relationship of protein glycosylation to compartmentalization and processing of mouse mammary tumor virus (MTV) glycoproteins has been examined in M1.54, a cloned line of MTV-infected rat hepatoma tissue culture cells. Previous work established that full maturation of MTV glycoproteins in this cell line requires dexamethasone, a synthetic glucocorticoid (Firestone, G. L., Payvar, F., and Yamamoto, K. R. (1982) Nature (Lond.) 300, 221-225). The ability to regulate production of the full complement of five mature membrane-associated and secreted viral glycoproteins from one initially synthesized precursor has been used to advantage in the present work. At concentrations of tunicamycin that specifically inhibit N-linked protein glycosylation, incorporation of [35S]methionine into total cellular and secreted protein is not detectably affected, MTV-specific mRNAs are produced normally, and the nonglycosylated form of the glycosylated viral precursor polyprotein accumulates within the cells. However, tunicamycin inhibits the site-specific cleavage of the glycosylated polyprotein and distribution of MTV polypeptides to the cell surface and extracellular fractions. Thus, when tunicamycin-treated cultures of M1.54 are exposed to dexamethasone and [35S]methionine, no labeled viral antigens are detected in the culture medium. Similarly, tunicamycin prevents the appearance of membrane-associated viral antigens that can be labeled externally by lactoperoxidase-mediated iodination and it protects the cells against the cytolytic effects of MTV-specific antiserum and complement. Taken together, these results are consistent with the view that while glycosylation of some proteins may be unessential for their compartmentalization and processing, it does appear to be correlated with proper maturation of others. The hormone-dependent maturation of MTV glycoproteins in M1.54 may be particularly useful for study of this latter class since glycosylation is stringently associated with their compartmentalization and cleavage. 相似文献
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Spliced exons of adenovirus late RNAs colocalize with snRNP in a specific nuclear domain 总被引:7,自引:5,他引:2
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《The Journal of cell biology》1996,135(2):303-314