Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1994 Mar;14(3):1743–1751. doi: 10.1128/mcb.14.3.1743

Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame.

D S Askew 1, J Li 1, J N Ihle 1
PMCID: PMC358532  PMID: 8114708

Abstract

The His-1 locus is a common site of viral insertion in murine myeloid leukemias induced by the wild mouse ecotropic retrovirus, CasBrM. In this report, we describe the cloning of a novel gene at the His-1 locus and show that His-1 expression is associated with the transformed phenotype. Northern (RNA) blot analysis identified His-1 transcripts in four transformed myeloid cell lines but in no normal tissues examined. Two of these cell lines were derived from retrovirus-induced myeloid leukemias that harbor integrated proviruses which drive His-1 gene expression by promoter insertion. The two other cell lines expressed a discrete 3-kb His-1 RNA that is derived from a novel gene consisting of three exons that span 6 kb on mouse chromosome 2. The His-1 gene is conserved as a single-copy sequence in multiple vertebrate species and is expressed as a spliced and polyadenylated RNA. A protein-coding region is not evident from analysis of the His-1 sequence because of the presence of multiple small open reading frames, none of which are greater than 219 bp. This lack of an extensive open reading frame is an unusual feature that is shared by other RNA molecules believed to function in the absence of translation.

Full text

PDF
1743

Images in this article

1744Image
on p.1744
1746Image
on p.1746
1748Image
on p.1748

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham K. M., Levin S. D., Marth J. D., Forbush K. A., Perlmutter R. M. Thymic tumorigenesis induced by overexpression of p56lck. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3977–3981. doi: 10.1073/pnas.88.9.3977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altman S. Ribonuclease P. Postscript. J Biol Chem. 1990 Nov 25;265(33):20053–20056. [PubMed] [Google Scholar]
  3. Askew D. S., Bartholomew C., Buchberg A. M., Valentine M. B., Jenkins N. A., Copeland N. G., Ihle J. N. His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia. Oncogene. 1991 Nov;6(11):2041–2047. [PubMed] [Google Scholar]
  4. Askew D. S., Bartholomew C., Ihle J. N. Insertional mutagenesis and the transformation of hematopoietic stem cells. Hematol Pathol. 1993;7(1):1–22. [PubMed] [Google Scholar]
  5. Azumi J. I., Sachs L. Chromosome mapping of the genes that control differentiation and malignancy in myeloid leukemic cells. Proc Natl Acad Sci U S A. 1977 Jan;74(1):253–257. doi: 10.1073/pnas.74.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Badley J. E., Bishop G. A., St John T., Frelinger J. A. A simple, rapid method for the purification of poly A+ RNA. Biotechniques. 1988 Feb;6(2):114–116. [PubMed] [Google Scholar]
  7. Bartel D. P., Szostak J. W. Isolation of new ribozymes from a large pool of random sequences [see comment]. Science. 1993 Sep 10;261(5127):1411–1418. doi: 10.1126/science.7690155. [DOI] [PubMed] [Google Scholar]
  8. Brannan C. I., Dees E. C., Ingram R. S., Tilghman S. M. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990 Jan;10(1):28–36. doi: 10.1128/mcb.10.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brockdorff N., Ashworth A., Kay G. F., McCabe V. M., Norris D. P., Cooper P. J., Swift S., Rastan S. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell. 1992 Oct 30;71(3):515–526. doi: 10.1016/0092-8674(92)90519-i. [DOI] [PubMed] [Google Scholar]
  10. Brown C. J., Hendrich B. D., Rupert J. L., Lafrenière R. G., Xing Y., Lawrence J., Willard H. F. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992 Oct 30;71(3):527–542. doi: 10.1016/0092-8674(92)90520-m. [DOI] [PubMed] [Google Scholar]
  11. Brunkow M. E., Tilghman S. M. Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes Dev. 1991 Jun;5(6):1092–1101. doi: 10.1101/gad.5.6.1092. [DOI] [PubMed] [Google Scholar]
  12. Cattanach B. M., Beechey C. V. Autosomal and X-chromosome imprinting. Dev Suppl. 1990:63–72. [PubMed] [Google Scholar]
  13. Cattaneo R. Different types of messenger RNA editing. Annu Rev Genet. 1991;25:71–88. doi: 10.1146/annurev.ge.25.120191.000443. [DOI] [PubMed] [Google Scholar]
  14. Cech T. R. Self-splicing of group I introns. Annu Rev Biochem. 1990;59:543–568. doi: 10.1146/annurev.bi.59.070190.002551. [DOI] [PubMed] [Google Scholar]
  15. Cech T. R. The chemistry of self-splicing RNA and RNA enzymes. Science. 1987 Jun 19;236(4808):1532–1539. doi: 10.1126/science.2438771. [DOI] [PubMed] [Google Scholar]
  16. Chang J. M., Metcalf D., Lang R. A., Gonda T. J., Johnson G. R. Nonneoplastic hematopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL-3) expression. Blood. 1989 May 1;73(6):1487–1497. [PubMed] [Google Scholar]
  17. Dean M., Cleveland J. L., Rapp U. R., Ihle J. N. Role of myc in the abrogation of IL3 dependence of myeloid FDC-P1 cells. Oncogene Res. 1987 Aug;1(3):279–296. [PubMed] [Google Scholar]
  18. Fickett J. W. Recognition of protein coding regions in DNA sequences. Nucleic Acids Res. 1982 Sep 11;10(17):5303–5318. doi: 10.1093/nar/10.17.5303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Forster A. C., Altman S. External guide sequences for an RNA enzyme. Science. 1990 Aug 17;249(4970):783–786. doi: 10.1126/science.1697102. [DOI] [PubMed] [Google Scholar]
  20. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Geliebter J., Zeff R. A., Schulze D. H., Pease L. R., Weiss E. H., Mellor A. L., Flavell R. A., Nathenson S. G. Interaction between Kb and Q4 gene sequences generates the Kbm6 mutation. Mol Cell Biol. 1986 Feb;6(2):645–652. doi: 10.1128/mcb.6.2.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gesteland R. F., Weiss R. B., Atkins J. F. Recoding: reprogrammed genetic decoding. Science. 1992 Sep 18;257(5077):1640–1641. doi: 10.1126/science.1529352. [DOI] [PubMed] [Google Scholar]
  23. Guthrie C. Messenger RNA splicing in yeast: clues to why the spliceosome is a ribonucleoprotein. Science. 1991 Jul 12;253(5016):157–163. doi: 10.1126/science.1853200. [DOI] [PubMed] [Google Scholar]
  24. Ihle J. N., Askew D. Origins and properties of hematopoietic growth factor-dependent cell lines. Int J Cell Cloning. 1989 Mar;7(2):68–91. doi: 10.1002/stem.5530070202. [DOI] [PubMed] [Google Scholar]
  25. Jackson R. J. Cytoplasmic regulation of mRNA function: the importance of the 3' untranslated region. Cell. 1993 Jul 16;74(1):9–14. doi: 10.1016/0092-8674(93)90290-7. [DOI] [PubMed] [Google Scholar]
  26. Katzav S., Martin-Zanca D., Barbacid M. vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells. EMBO J. 1989 Aug;8(8):2283–2290. doi: 10.1002/j.1460-2075.1989.tb08354.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lammie G. A., Smith R., Silver J., Brookes S., Dickson C., Peters G. Proviral insertions near cyclin D1 in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms. Oncogene. 1992 Dec;7(12):2381–2387. [PubMed] [Google Scholar]
  29. Lavigueur A., Bernstein A. p53 transgenic mice: accelerated erythroleukemia induction by Friend virus. Oncogene. 1991 Dec;6(12):2197–2201. [PubMed] [Google Scholar]
  30. Lazo P. A., Lee J. S., Tsichlis P. N. Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas. Proc Natl Acad Sci U S A. 1990 Jan;87(1):170–173. doi: 10.1073/pnas.87.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Leder A., Pattengale P. K., Kuo A., Stewart T. A., Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986 May 23;45(4):485–495. doi: 10.1016/0092-8674(86)90280-1. [DOI] [PubMed] [Google Scholar]
  32. Matsunaga E., Umeno M., Gonzalez F. J. The rat P450 IID subfamily: complete sequences of four closely linked genes and evidence that gene conversions maintained sequence homogeneity at the heme-binding region of the cytochrome P450 active site. J Mol Evol. 1990 Feb;30(2):155–169. doi: 10.1007/BF02099942. [DOI] [PubMed] [Google Scholar]
  33. Noller H. F., Hoffarth V., Zimniak L. Unusual resistance of peptidyl transferase to protein extraction procedures. Science. 1992 Jun 5;256(5062):1416–1419. doi: 10.1126/science.1604315. [DOI] [PubMed] [Google Scholar]
  34. Piccirilli J. A., McConnell T. S., Zaug A. J., Noller H. F., Cech T. R. Aminoacyl esterase activity of the Tetrahymena ribozyme. Science. 1992 Jun 5;256(5062):1420–1424. doi: 10.1126/science.1604316. [DOI] [PubMed] [Google Scholar]
  35. Robertson D. L., Joyce G. F. Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature. 1990 Mar 29;344(6265):467–468. doi: 10.1038/344467a0. [DOI] [PubMed] [Google Scholar]
  36. Sachs A. B. Messenger RNA degradation in eukaryotes. Cell. 1993 Aug 13;74(3):413–421. doi: 10.1016/0092-8674(93)80043-e. [DOI] [PubMed] [Google Scholar]
  37. Schwarzbaum S., Halpern R., Diamond B. The generation of macrophage-like cell lines by transfection with SV40 origin defective DNA. J Immunol. 1984 Mar;132(3):1158–1162. [PubMed] [Google Scholar]
  38. Shapiro M. B., Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987 Sep 11;15(17):7155–7174. doi: 10.1093/nar/15.17.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tavianini M. A., Hayes T. E., Magazin M. D., Minth C. D., Dixon J. E. Isolation, characterization, and DNA sequence of the rat somatostatin gene. J Biol Chem. 1984 Oct 10;259(19):11798–11803. [PubMed] [Google Scholar]
  40. Tsichlis P. N., Lazo P. A. Virus-host interactions and the pathogenesis of murine and human oncogenic retroviruses. Curr Top Microbiol Immunol. 1991;171:95–171. doi: 10.1007/978-3-642-76524-7_5. [DOI] [PubMed] [Google Scholar]
  41. Tsukamoto A. S., Grosschedl R., Guzman R. C., Parslow T., Varmus H. E. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell. 1988 Nov 18;55(4):619–625. doi: 10.1016/0092-8674(88)90220-6. [DOI] [PubMed] [Google Scholar]
  42. Uberbacher E. C., Mural R. J. Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11261–11265. doi: 10.1073/pnas.88.24.11261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wickens M. How the messenger got its tail: addition of poly(A) in the nucleus. Trends Biochem Sci. 1990 Jul;15(7):277–281. doi: 10.1016/0968-0004(90)90054-f. [DOI] [PubMed] [Google Scholar]
  44. van Lohuizen M., Berns A. Tumorigenesis by slow-transforming retroviruses--an update. Biochim Biophys Acta. 1990 Dec 11;1032(2-3):213–235. doi: 10.1016/0304-419x(90)90005-l. [DOI] [PubMed] [Google Scholar]
  45. van Lohuizen M., Verbeek S., Krimpenfort P., Domen J., Saris C., Radaszkiewicz T., Berns A. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell. 1989 Feb 24;56(4):673–682. doi: 10.1016/0092-8674(89)90589-8. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES