Intracisternal A-particle gene expression in normal mouse thymus tissue: gene products and strain-related variability.

Abstract

Intracisternal A-particle (IAP)-specific sequences were 5-to 10-fold enriched in polyadenylated RNA from BALB/cJ thymus as compared with RNAs from liver, spleen, and kidney. The major transcripts of 7.2 and 5.4 kilobases were the same size as those found in an TAP-rich neuroblastoma cell line. The absolute levels and proportions of these transcripts varied in thymuses from mice of different inbred strains. With antiserum prepared against p73, the main IAP structural protein, several size classes of IAP-related proteins were immunoprecipitated from extracts of thymus cells incubated with [35S]methionine; these included p73 itself and a group of polypeptides in the size range of 114 to 120 kilodaltons (pll4-pl20). The inbred strains showed marked characteristic differences in the electrophoretic patterns of their IAP-related proteins. Earlier studies showed that the 7.2-kilobase RNA from neuroblastoma IAPs coded for p73 in a cell-free translation system. Correlations between the RNA and protein patterns in thymuses of the different inbred strains indicated that 5.4-kilobase RNA gives rise to the pll4-pl20 polypeptides. Metabolically labeled p120 was found to include methionine-containing tryptic peptides of p73 plus additional peptides consistent with its larger size. In vivo labeling kinetics showed that the pll4-pl20 polypeptides were not major precursors of p73 in intact neuroblastoma cells. This study shows that IAP gene expression in mouse thymus is genetically determined and that a novel class of IAP-related polypeptides can be expressed independently of the major particle structural protein.Intracisternal A-particles (IAPs) are retrovirus-like entities found in many types of mouse tumor cells (20,45). They contain a group-specific internal structural protein, p73 (20,32), and a DNA polymerase activity with properties of reverse transcriptase (42, 43). The isolated particles also contain specific polyadenylated [poly(A)] RNAs (30) ranging in size from 7.2 to about 3.5 kilobases (kb) (34,36,41). These RNA species, which are related to one another in sequence, vary in relative proportion in particles isolated from different tumor sources. Endogenous provirus-like elements homologous to the IAP-associated RNAs ("IAP genes") are reiterated 1,000-fold per haploid genome in Mus musculus (28). The full-size genetic unit is 7.3 kb in length and is colinear with the 7.2-kb transcript (21). Shorter elements with internal deletions are also found (21, 34), and one group of these, the so-called type IT elements (40), are known to give rise to some of the shorter IAP-specific RNAs (34, 41). The IAP genetic elements share many structural properties with integrated retroviral proviruses and certain transposable elements in Drosophila spp. and yeasts (8a). Recently, IAP genes have been found to appear in novel locations in the genome of certain IAP-rich BALB/c mouse myeloma and hybridoma cell lines and to affect the function of genes at the various target sites (5,7,9,10,18,19,41). Thus, on occasion they can act as mobile e...

Differential effects of retroviral long terminal repeats on interleukin-3 gene expression and autocrine transformation

“…Organs and cells which express low levels of IAPs Acute oncogenic retroviruses, which contain an oncogene, include: spleen, muscle, pancreas, ovary, thymus, placenta, cause cancer after a short period of time post-infection of a macrophage and fibroblast cells. 14,27 IAP expression is under susceptible host, ranging from one to a few months. Chronic genetic control in non-neoplastic cells.…”

“…Chronic oncogenic retroviruses can cause cancer transcripts. [27][28][29] via proviral insertional activation of flanking cellular genes. 2,3 Murine plasmacytoma cells (B plasma immunoglobulinThe novel insertion of the viral sequences into host cell DNAs secreting tumor cells) generally express higher levels of IAP can have profound effects on the regulation of the adjacent mRNA transcripts than normal activated B or T lymphocytes.…”

Glucose induces intracisternal type A retroviral gene transcription and translation in pancreatic beta cells.

“…Each tube was vortexed for 3 rain and centrifuged at 800 g for 10 rain at 4°C. The supernatant fi'action was used for immunoprecipitation (see below (5). Briefly, the extract proteins were treated at 100°C with 2-ME in the presence of SDS, after which the 2-ME was reacted with a slight excess of iodoacetamide.…”

“…A subgenomic 5.4 kb mRNA encodes a family of higher-molecular mass peptides (114-120 kD), which are structurally related to p73, but which apparently are not major precursors (5). In the B6 thymus, this novel class of IAP-related polypeptides (pl14-p120) can be expressed independently of p73, which is not expressed (5). In this study, we asked whether glucose might exert differential control of expression of IAP genomes in beta cells of diabetes-susceptible vs. -resistant inbred strains of mice.…”

“…The mRNA for p73 is transcribed from the full-length genetic unit (7.3 kb) as colinear 7.2 kb transcripts (4). A subgenomic 5.4 kb mRNA encodes a family of higher-molecular mass peptides (114-120 kD), which are structurally related to p73, but which apparently are not major precursors (5). In the B6 thymus, this novel class of IAP-related polypeptides (pl14-p120) can be expressed independently of p73, which is not expressed (5).…”