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Gene Review

A130040M12Rik  -  RIKEN cDNA A130040M12 gene

Mus musculus

Synonyms: CA782090, H3053C11, VL30
 
 
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Disease relevance of A130040M12Rik

  • The mouse genome contains multiple copies of a dispersed gene family known individually as VL30 genes which are thought to be associated with retroviruses [1].
  • In contrast, nine additional clones, including an AKR-type murine leukemia provirus DNA clone, contained no detectable VL30 sequence elements and were complementary to poly(A)+RNA species whose relative concentration was essentially constant in quiescent and EGF-stimulated cells [2].
  • Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells promotes metastasis in an immunodeficient mouse model [3].
  • A family of dispersed, moderately repeated mouse genetic elements is expressed as retrovirus-like 30S RNA species (VL30 RNA) which can be transmitted to other cells when packaged as a pseudovirion complex by murine leukemia viruses (MuLV) [4].
  • Three very basic questions have existed about the VL30 element sequences found in sarcoma viruses: (i) how did they become recombined, (ii) what are their exact boundaries, and (iii) why are they there [5]?
 

High impact information on A130040M12Rik

  • Stimulated by recent reports of the similarity between retroviruses and transposons (from which retroviruses may have evolved), and in particular by the recognition that both types of genetic elements are characterized by a large terminal repeat (LTR), we set out to determine whether the VL30 genes are also distinguished by this property [1].
  • Using cloned DNAs from a mouse gene library and heteroduplex analysis, we have now found that the VL30 genes do indeed carry terminal direct repeats 400 base pairs long [1].
  • Expression of VL30 in both male and female gonads was shown to be greatly stimulated by external administration of gonadotropins [6].
  • Here, we report that VL30 retrotransposons are specifically expressed in steroidogenic cells within all four endocrine tissues engaged in synthesis of steroid hormones in response to the respective pituitary-derived trophic hormones [6].
  • Alternative cis-acting promoter elements derived from VL30 retroelements have been effective in expressing tissue-specific transgene expression in vivo in nonerythroid cells [7].
 

Chemical compound and disease context of A130040M12Rik

  • The VL30 provirus was integrated into the rat genome, expressed at high levels, and its transcription induced 40-fold by dexamethasone, VL30 RNA was detected in hepatoma cells even without selection for the expression of the amino-3'-glycosyl phosphotransferase (neo) gene, which was co-transferred with a MoMLV retrovirus [8].
 

Biological context of A130040M12Rik

  • The mouse genome has multiple copies of VL30 retroelements that are developmentally regulated, and mouse cells contain VL30 RNAs that have normal and pathological roles in gene regulation [9].
  • Complete nucleotide sequence of a mouse VL30 retro-element [10].
  • These findings suggest that recombinations have played a role in generating the diverse population of VL30-associated LTRs [11].
  • Deletion analysis of the VL30 long-terminal-repeat U3 region showed that a minimal 53-base-pair segment is required in cis for oncogene activation of transcription [12].
  • We found that VL30 gene expression varied in different mouse cell lines such that C3H cell lines had very low levels of VL30 transcripts relative to NIH 3T3 cell lines [13].
 

Anatomical context of A130040M12Rik

  • However, Southern analysis showed that both cell lines had about the same number of VL30 genes homologous to our probe and that the position of the majority of these genes was conserved [13].
  • Isolation of cellular genes differentially expressed in mouse NIH 3T3 cells and a simian virus 40-transformed derivative: growth-specific expression of VL30 genes [13].
  • A retrovirus-like 30S (VL30) gene induced in mouse epidermis after a single application of 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a model gene to define mechanisms of transcriptional regulation in keratinocytes [14].
  • The non-responsiveness correlated with a reduced complex formation between a VL30 RRE and endogenously expressed nuclear factors present in skin fibroblasts [15].
  • Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors [16].
 

Associations of A130040M12Rik with chemical compounds

  • Preliminary sequence analysis of four of the 11 cDNAs suggests that two cDNAs represent previously undescribed genes while two others correspond to the mouse VL30 retrovirus-like element and the mouse homolog of chondroitin sulfate proteoglycan core protein [17].
  • A single VL30 element present in the RVL-3 cell line was transcriptionally induced by both epidermal growth factor (EGF) and the protein kinase C (pkC) activators 12-O-tetradecanoylphorbol-13-acetate (TPA) and sn-1,2-dioctanoylglycerol within 5 min of stimulation [18].
  • VL30-related transcripts were slightly decreased after TCPOBOP, but they were markedly increased at days 1 and 2 following CCl4 [19].
  • The calcium ionophore A23187 induced mRNA levels for MTs as well as VL30 [20].
  • Northern blot analysis of polyadenylated liver RNA samples indicated an increase in the levels of RNA homologous to Moloney murine leukemia virus and intracisternal A particle sequences but no significant change in the level of VL30 retrovirus-related RNA in the samples from mice fed methyl-deficient diets [21].
 

Analytical, diagnostic and therapeutic context of A130040M12Rik

  • Analysis of cellular RNA by Northern blotting and nuclease S1 protection assays indicates that the expression of two cellular RNA species increases with kinetics similar to v-ras: v-sis-related RNA and retrovirus-related VL30 RNA [22].
  • Immunohistochemistry and time-kinetic studies on mRNA levels in mouse epidermis showed that the increase in MT and VL30 RNAs coincide in time with a TPA-induced transient block in basal cell proliferation (3-12 h after TPA treatment) [20].
  • Southern blot analyses using reduced stringency hybridization conditions have been employed to search for sequence homologies between rodent VL30 genes and murine leukemia virus (MuLV) proviruses [23].
  • These results indicate that great care should be given to the transfer of unwanted passengers, like VL30, present in retroviral packaging cell lines like the psi 2 cells, which are currently being used for gene therapy [8].
  • However, VL30 RNAs are efficiently packaged into MLV particles that are propagated in cell culture [16].

References

  1. Terminal direct repeats in a retrovirus-like repeated mouse gene family. Keshet, E., Shaul, Y. Nature (1981) [Pubmed]
  2. Polyadenylylated RNA complementary to a mouse retrovirus-like multigene family is rapidly and specifically induced by epidermal growth factor stimulation of quiescent cells. Foster, D.N., Schmidt, L.J., Hodgson, C.P., Moses, H.L., Getz, M.J. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  3. Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells promotes metastasis in an immunodeficient mouse model. Song, X., Wang, B., Bromberg, M., Hu, Z., Konigsberg, W., Garen, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. A novel approach to cloning transcriptionally active retrovirus-like genetic elements from mouse cells. Carter, A.T., Norton, J.D., Avery, R.J. Nucleic Acids Res. (1983) [Pubmed]
  5. Anoxia-inducible rat VL30 elements and their relationship to ras-containing sarcoma viruses. Firulli, B.A., Anderson, G.R., Stoler, D.L., Estes, S.D. J. Virol. (1993) [Pubmed]
  6. Transcriptional activation of mouse retrotransposons in vivo: specific expression in steroidogenic cells in response to trophic hormones. Schiff, R., Itin, A., Keshet, E. Genes Dev. (1991) [Pubmed]
  7. BVL-1-like VL30 promoter sustains long-term expression in erythroid progenitor cells. Staplin, W.R., Knezetic, J.A. Blood (2003) [Pubmed]
  8. Efficient packaging of a specific VL30 retroelement by psi 2 cells which produce MoMLV recombinant retroviruses. Hatzoglou, M., Hodgson, C.P., Mularo, F., Hanson, R.W. Hum. Gene Ther. (1990) [Pubmed]
  9. Roles of PSF protein and VL30 RNA in reversible gene regulation. Song, X., Sun, Y., Garen, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Complete nucleotide sequence of a mouse VL30 retro-element. Adams, S.E., Rathjen, P.D., Stanway, C.A., Fulton, S.M., Malim, M.H., Wilson, W., Ogden, J., King, L., Kingsman, S.M., Kingsman, A.J. Mol. Cell. Biol. (1988) [Pubmed]
  11. Diverse long terminal repeats are associated with murine retroviruslike (VL30) elements. Itin, A., Keshet, E. Mol. Cell. Biol. (1986) [Pubmed]
  12. ras oncogene activation of a VL30 transcriptional element is linked to transformation. Owen, R.D., Bortner, D.M., Ostrowski, M.C. Mol. Cell. Biol. (1990) [Pubmed]
  13. Isolation of cellular genes differentially expressed in mouse NIH 3T3 cells and a simian virus 40-transformed derivative: growth-specific expression of VL30 genes. Singh, K., Saragosti, S., Botchan, M. Mol. Cell. Biol. (1985) [Pubmed]
  14. Identification of protein-binding sequences mediating constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced VL30 transcription in cultured mouse and human keratinocytes. Bohm, S. J. Biol. Chem. (1991) [Pubmed]
  15. The long terminal repeat of VL30 retrotransposons contains sequences that determine retinoic acid-induced transcription in cultured keratinocytes. Islam, T.C., Bugge, T.H., Bohm, S. J. Biol. Chem. (1993) [Pubmed]
  16. Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors. López-Lastra, M., Ulrici, S., Gabus, C., Darlix, J.L. J. Virol. (1999) [Pubmed]
  17. Isolation and characterization of glucocorticoid- and cyclic AMP-induced genes in T lymphocytes. Harrigan, M.T., Baughman, G., Campbell, N.F., Bourgeois, S. Mol. Cell. Biol. (1989) [Pubmed]
  18. Independent transcriptional regulation of a single VL30 element by epidermal growth factor and activators of protein kinase C. Rodland, K.D., Muldoon, L.L., Dinh, T.H., Magun, B.E. Mol. Cell. Biol. (1988) [Pubmed]
  19. Factors influencing the expression of endogenous retrovirus-related sequences in the liver of B6C3 mice. Dragani, T.A., Manenti, G., Della Porta, G., Weinstein, I.B. Cancer Res. (1987) [Pubmed]
  20. Isolation and characterization of complementary DNA clones corresponding to genes induced in mouse epidermis in vivo by tumor promoters. Bohm, S., Berghard, A., Pereswetoff-Morath, C., Toftgård, R. Cancer Res. (1990) [Pubmed]
  21. Altered expression of retrovirus-like sequences and cellular oncogenes in mice fed methyl-deficient diets. Hsieh, L.L., Wainfan, E., Hoshina, S., Dizik, M., Weinstein, I.B. Cancer Res. (1989) [Pubmed]
  22. Rapid and selective alterations in the expression of cellular genes accompany conditional transcription of Ha-v-ras in NIH 3T3 cells. Owen, R.D., Ostrowski, M.C. Mol. Cell. Biol. (1987) [Pubmed]
  23. Discrete regions of sequence homology between cloned rodent VL30 genetic elements and AKV-related MuLV provirus genomes. Giri, C.P., Hodgson, C.P., Elder, P.K., Courtney, M.G., Getz, M.J. Nucleic Acids Res. (1983) [Pubmed]
 
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