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. 1990 Jan;10(1):28–36. doi: 10.1128/mcb.10.1.28

The product of the H19 gene may function as an RNA.

C I Brannan 1, E C Dees 1, R S Ingram 1, S M Tilghman 1
PMCID: PMC360709  PMID: 1688465

Abstract

The mouse H19 gene was identified as an abundant hepatic fetal-specific mRNA under the transcriptional control of a trans-acting locus termed raf. The protein this gene encoded was not apparent from an analysis of its nucleotide sequence, since the mRNA contained multiple translation termination signals in all three reading frames. As a means of assessing which of the 35 small open reading frames might be important to the function of the gene, the human H19 gene was cloned and sequenced. Comparison of the two homologs revealed no conserved open reading frame. Cellular fractionation showed that H19 RNA is cytoplasmic but not associated with the translational machinery. Instead, it is located in a particle with a sedimentation coefficient of approximately 28S. Despite the fact that it is transcribed by RNA polymerase II and is spliced and polyadenylated, we suggest that the H19 RNA is not a classical mRNA. Instead, the product of this unusual gene may be an RNA molecule.

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Selected References

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  1. Baker M. E. Evolution of alpha-fetoprotein: sequence comparisons among AFP species and with albumin species. Tumour Biol. 1988;9(2-3):123–136. doi: 10.1159/000217553. [DOI] [PubMed] [Google Scholar]
  2. Belayew A., Tilghman S. M. Genetic analysis of alpha-fetoprotein synthesis in mice. Mol Cell Biol. 1982 Nov;2(11):1427–1435. doi: 10.1128/mcb.2.11.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  4. Butnick N. Z., Miyamoto C., Chizzonite R., Cullen B. R., Ju G., Skalka A. M. Regulation of the human c-myc gene: 5' noncoding sequences do not affect translation. Mol Cell Biol. 1985 Nov;5(11):3009–3016. doi: 10.1128/mcb.5.11.3009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clare J., Farabaugh P. Nucleotide sequence of a yeast Ty element: evidence for an unusual mechanism of gene expression. Proc Natl Acad Sci U S A. 1985 May;82(9):2829–2833. doi: 10.1073/pnas.82.9.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  7. Eckert R. L., Green H. Structure and evolution of the human involucrin gene. Cell. 1986 Aug 15;46(4):583–589. doi: 10.1016/0092-8674(86)90884-6. [DOI] [PubMed] [Google Scholar]
  8. Fini M. E., Bendena W. G., Pardue M. L. Unusual behavior of the cytoplasmic transcript of hsr omega: an abundant, stress-inducible RNA that is translated but yields no detectable protein product. J Cell Biol. 1989 Jun;108(6):2045–2057. doi: 10.1083/jcb.108.6.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hann S. R., King M. W., Bentley D. L., Anderson C. W., Eisenman R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell. 1988 Jan 29;52(2):185–195. doi: 10.1016/0092-8674(88)90507-7. [DOI] [PubMed] [Google Scholar]
  10. Hinnebusch A. G. Evidence for translational regulation of the activator of general amino acid control in yeast. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6442–6446. doi: 10.1073/pnas.81.20.6442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jacks T., Varmus H. E. Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. Science. 1985 Dec 13;230(4731):1237–1242. doi: 10.1126/science.2416054. [DOI] [PubMed] [Google Scholar]
  12. Kioussis D., Eiferman F., van de Rijn P., Gorin M. B., Ingram R. S., Tilghman S. M. The evolution of alpha-fetoprotein and albumin. II. The structures of the alpha-fetoprotein and albumin genes in the mouse. J Biol Chem. 1981 Feb 25;256(4):1960–1967. [PubMed] [Google Scholar]
  13. Kleene K. C., Distel R. J., Hecht N. B. Translational regulation and deadenylation of a protamine mRNA during spermiogenesis in the mouse. Dev Biol. 1984 Sep;105(1):71–79. doi: 10.1016/0012-1606(84)90262-8. [DOI] [PubMed] [Google Scholar]
  14. Konieczny S. F., Emerson C. P., Jr Differentiation, not determination, regulates muscle gene activation: transfection of troponin I genes into multipotential and muscle lineages of 10T1/2 cells. Mol Cell Biol. 1985 Sep;5(9):2423–2432. doi: 10.1128/mcb.5.9.2423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kozak M. Bifunctional messenger RNAs in eukaryotes. Cell. 1986 Nov 21;47(4):481–483. doi: 10.1016/0092-8674(86)90609-4. [DOI] [PubMed] [Google Scholar]
  16. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kozak M. Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes. Nucleic Acids Res. 1981 Oct 24;9(20):5233–5252. doi: 10.1093/nar/9.20.5233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lee J. Y., Engelke D. R. Partial characterization of an RNA component that copurifies with Saccharomyces cerevisiae RNase P. Mol Cell Biol. 1989 Jun;9(6):2536–2543. doi: 10.1128/mcb.9.6.2536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mangin M., Ikeda K., Dreyer B. E., Broadus A. E. Isolation and characterization of the human parathyroid hormone-like peptide gene. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2408–2412. doi: 10.1073/pnas.86.7.2408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Messing J., Gronenborn B., Müller-Hill B., Hans Hopschneider P. Filamentous coliphage M13 as a cloning vehicle: insertion of a HindII fragment of the lac regulatory region in M13 replicative form in vitro. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3642–3646. doi: 10.1073/pnas.74.9.3642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Minghetti P. P., Law S. W., Dugaiczyk A. The rate of molecular evolution of alpha-fetoprotein approaches that of pseudogenes. Mol Biol Evol. 1985 Jul;2(4):347–358. doi: 10.1093/oxfordjournals.molbev.a040350. [DOI] [PubMed] [Google Scholar]
  23. Minty A. J., Caravatti M., Robert B., Cohen A., Daubas P., Weydert A., Gros F., Buckingham M. E. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed] [Google Scholar]
  24. Olsson M., Lindahl G., Ruoslahti E. Genetic control of alpha-fetoprotein synthesis in the mouse. J Exp Med. 1977 Apr 1;145(4):819–827. doi: 10.1084/jem.145.4.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pachnis V., Belayew A., Tilghman S. M. Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5523–5527. doi: 10.1073/pnas.81.17.5523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pachnis V., Brannan C. I., Tilghman S. M. The structure and expression of a novel gene activated in early mouse embryogenesis. EMBO J. 1988 Mar;7(3):673–681. doi: 10.1002/j.1460-2075.1988.tb02862.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Powell L. M., Wallis S. C., Pease R. J., Edwards Y. H., Knott T. J., Scott J. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell. 1987 Sep 11;50(6):831–840. doi: 10.1016/0092-8674(87)90510-1. [DOI] [PubMed] [Google Scholar]
  28. Reddy R. Compilation of small RNA sequences. Nucleic Acids Res. 1988;16 (Suppl):r71–r85. doi: 10.1093/nar/16.suppl.r71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schneider R. J., Weinberger C., Shenk T. Adenovirus VAI RNA facilitates the initiation of translation in virus-infected cells. Cell. 1984 May;37(1):291–298. doi: 10.1016/0092-8674(84)90325-8. [DOI] [PubMed] [Google Scholar]
  31. Siliciano P. G., Jones M. H., Guthrie C. Saccharomyces cerevisiae has a U1-like small nuclear RNA with unexpected properties. Science. 1987 Sep 18;237(4821):1484–1487. doi: 10.1126/science.3306922. [DOI] [PubMed] [Google Scholar]
  32. Thireos G., Penn M. D., Greer H. 5' untranslated sequences are required for the translational control of a yeast regulatory gene. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5096–5100. doi: 10.1073/pnas.81.16.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tiemeier D. C., Tilghman S. M., Leder P. Purification and cloning of a mouse ribosomal gene fragment in coliphage lambda. Gene. 1977;2(3-4):173–191. doi: 10.1016/0378-1119(77)90016-6. [DOI] [PubMed] [Google Scholar]
  35. Tzamarias D., Roussou I., Thireos G. Coupling of GCN4 mRNA translational activation with decreased rates of polypeptide chain initiation. Cell. 1989 Jun 16;57(6):947–954. doi: 10.1016/0092-8674(89)90333-4. [DOI] [PubMed] [Google Scholar]
  36. Zakeri Z. F., Ponzetto C., Wolgemuth D. J. Translational regulation of the novel haploid-specific transcripts for the c-abl proto-oncogene and a member of the 70 kDa heat-shock protein gene family in the male germ line. Dev Biol. 1988 Feb;125(2):417–422. doi: 10.1016/0012-1606(88)90222-9. [DOI] [PubMed] [Google Scholar]

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