Abstract
The mammalian prion protein (PrPc) is a cellular protein of unknown function, an altered isoform of which (PrPsc) is a component of the infectious particle (prion) thought to be responsible for spongiform encephalopathies in humans and animals. The evolutionary conservation of the PrP gene has been reported in the genomes of many vertebrates as well as certain invertebrates. In the genome of nematode Caenorhabditis elegans, the sequence capable of hybridizing with the mammalian PrP cDNA probe has been demonstrated, predicting the presence of the PrP gene homologue in C.elegans. In this study, Southern analysis with the hamster PrP cDNA (HaPrP) probe confirmed the previous observation. Moreover, Northern analysis revealed that the sequence is actively transcribed in adult worms. Thus, we screened C.elegans cDNA libraries with the HaPrP probe and isolated a cDNA that hybridizes to the same sequence in C.elegans that hybridized with the HaPrP probe in the Southern and Northern analyses. The deduced amino acid sequence of this cDNA, however, is substantially homologous with heterogeneous nuclear ribonucleoprotein (hnRNP) core proteins rather than mammalian PrPc. The hnRNPs contain the glycine-rich domain in the C-terminal half of the molecule, which also seemed to be in PrPc at the N-terminal half of the molecule. Both of the glycine-rich domains are composed of tracts with high G + C content, indicating that these tracts may due to the hybridizing signals. These results suggest that this cDNA clone is derived from a novel hnRNP gene homologue in C.elegans but not from a predicted PrP gene homologue.
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- Ball E. E., Rehm E. J., Goodman C. S. Cloning of a grasshopper cDNA coding for a protein homologous to the A1, A2/B1 proteins of mammalian hnRNP. Nucleic Acids Res. 1991 Jan 25;19(2):397–397. doi: 10.1093/nar/19.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Basler K., Oesch B., Scott M., Westaway D., Wälchli M., Groth D. F., McKinley M. P., Prusiner S. B., Weissmann C. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell. 1986 Aug 1;46(3):417–428. doi: 10.1016/0092-8674(86)90662-8. [DOI] [PubMed] [Google Scholar]
- Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burd C. G., Swanson M. S., Görlach M., Dreyfuss G. Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9788–9792. doi: 10.1073/pnas.86.24.9788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buvoli M., Biamonti G., Tsoulfas P., Bassi M. T., Ghetti A., Riva S., Morandi C. cDNA cloning of human hnRNP protein A1 reveals the existence of multiple mRNA isoforms. Nucleic Acids Res. 1988 May 11;16(9):3751–3770. doi: 10.1093/nar/16.9.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chesebro B., Race R., Wehrly K., Nishio J., Bloom M., Lechner D., Bergstrom S., Robbins K., Mayer L., Keith J. M. Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature. 1985 May 23;315(6017):331–333. doi: 10.1038/315331a0. [DOI] [PubMed] [Google Scholar]
- Cobianchi F., SenGupta D. N., Zmudzka B. Z., Wilson S. H. Structure of rodent helix-destabilizing protein revealed by cDNA cloning. J Biol Chem. 1986 Mar 15;261(8):3536–3543. [PubMed] [Google Scholar]
- Goldmann W., Hunter N., Foster J. D., Salbaum J. M., Beyreuther K., Hope J. Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2476–2480. doi: 10.1073/pnas.87.7.2476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldmann W., Hunter N., Martin T., Dawson M., Hope J. Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. J Gen Virol. 1991 Jan;72(Pt 1):201–204. doi: 10.1099/0022-1317-72-1-201. [DOI] [PubMed] [Google Scholar]
- Harris D. A., Falls D. L., Johnson F. A., Fischbach G. D. A prion-like protein from chicken brain copurifies with an acetylcholine receptor-inducing activity. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7664–7668. doi: 10.1073/pnas.88.17.7664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haynes S. R., Johnson D., Raychaudhuri G., Beyer A. L. The Drosophila Hrb87F gene encodes a new member of the A and B hnRNP protein group. Nucleic Acids Res. 1991 Jan 11;19(1):25–31. doi: 10.1093/nar/19.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haynes S. R., Rebbert M. L., Mozer B. A., Forquignon F., Dawid I. B. pen repeat sequences are GGN clusters and encode a glycine-rich domain in a Drosophila cDNA homologous to the rat helix destabilizing protein. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1819–1823. doi: 10.1073/pnas.84.7.1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kay B. K., Sawhney R. K., Wilson S. H. Potential for two isoforms of the A1 ribonucleoprotein in Xenopus laevis. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1367–1371. doi: 10.1073/pnas.87.4.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kretzschmar H. A., Stowring L. E., Westaway D., Stubblebine W. H., Prusiner S. B., Dearmond S. J. Molecular cloning of a human prion protein cDNA. DNA. 1986 Aug;5(4):315–324. doi: 10.1089/dna.1986.5.315. [DOI] [PubMed] [Google Scholar]
- Liao Y. C., Lebo R. V., Clawson G. A., Smuckler E. A. Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications. Science. 1986 Jul 18;233(4761):364–367. doi: 10.1126/science.3014653. [DOI] [PubMed] [Google Scholar]
- Liao Y. C., Tokes Z., Lim E., Lackey A., Woo C. H., Button J. D., Clawson G. A. Cloning of rat "prion-related protein" cDNA. Lab Invest. 1987 Oct;57(4):370–374. [PubMed] [Google Scholar]
- Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
- Locht C., Chesebro B., Race R., Keith J. M. Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6372–6376. doi: 10.1073/pnas.83.17.6372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oesch B., Westaway D., Prusiner S. B. Prion protein genes: evolutionary and functional aspects. Curr Top Microbiol Immunol. 1991;172:109–124. doi: 10.1007/978-3-642-76540-7_7. [DOI] [PubMed] [Google Scholar]
- Oesch B., Westaway D., Wälchli M., McKinley M. P., Kent S. B., Aebersold R., Barry R. A., Tempst P., Teplow D. B., Hood L. E. A cellular gene encodes scrapie PrP 27-30 protein. Cell. 1985 Apr;40(4):735–746. doi: 10.1016/0092-8674(85)90333-2. [DOI] [PubMed] [Google Scholar]
- Petryniak B., Staudt L. M., Postema C. E., McCormack W. T., Thompson C. B. Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1099–1103. doi: 10.1073/pnas.87.3.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prusiner S. B. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9;216(4542):136–144. doi: 10.1126/science.6801762. [DOI] [PubMed] [Google Scholar]
- Roberts L. The worm project. Science. 1990 Jun 15;248(4961):1310–1313. doi: 10.1126/science.2356467. [DOI] [PubMed] [Google Scholar]
- 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]
- Sulston J. E., Brenner S. The DNA of Caenorhabditis elegans. Genetics. 1974 May;77(1):95–104. doi: 10.1093/genetics/77.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waterston R., Martin C., Craxton M., Huynh C., Coulson A., Hillier L., Durbin R., Green P., Shownkeen R., Halloran N. A survey of expressed genes in Caenorhabditis elegans. Nat Genet. 1992 May;1(2):114–123. doi: 10.1038/ng0592-114. [DOI] [PubMed] [Google Scholar]
- Weissmann C. A 'unified theory' of prion propagation. Nature. 1991 Aug 22;352(6337):679–683. doi: 10.1038/352679a0. [DOI] [PubMed] [Google Scholar]
- Westaway D., Goodman P. A., Mirenda C. A., McKinley M. P., Carlson G. A., Prusiner S. B. Distinct prion proteins in short and long scrapie incubation period mice. Cell. 1987 Nov 20;51(4):651–662. doi: 10.1016/0092-8674(87)90134-6. [DOI] [PubMed] [Google Scholar]
- Westaway D., Prusiner S. B. Conservation of the cellular gene encoding the scrapie prion protein. Nucleic Acids Res. 1986 Mar 11;14(5):2035–2044. doi: 10.1093/nar/14.5.2035. [DOI] [PMC free article] [PubMed] [Google Scholar]



