Abstract
In situ hybridization has revealed a striking subnuclear distribution of c-myc RNA transcripts. A major fraction of the sense-strand nuclear c-myc transcripts was localized to the nucleoli. myc intron 1-containing RNAs were noticeably absent from nucleoli, accumulating instead in the nucleoplasm. The localization of myc RNA to nucleoli was shown to be common to a number of diverse cell types, including primary Sertoli cells and several cell lines. Furthermore, nucleolar localization was not restricted to c-myc and N-myc and myoD transcripts also displayed this phenomenon. In contrast, gamma-actin or lactate dehydrogenase transcripts did not display nucleolar localization. These observations suggest a new role for the nucleolus in transport and/or turnover of potential mRNAs.
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- Anastassova-Kristeva M. The nucleolar cycle in man. J Cell Sci. 1977 Jun;25:103–110. doi: 10.1242/jcs.25.1.103. [DOI] [PubMed] [Google Scholar]
- Bachellerie J. P., Michot B., Raynal F. Recognition signals for mouse pre-rRNA processing. A potential role for U3 nucleolar RNA. Mol Biol Rep. 1983 May;9(1-2):79–86. doi: 10.1007/BF00777477. [DOI] [PubMed] [Google Scholar]
- Blau H. M., Pavlath G. K., Hardeman E. C., Chiu C. P., Silberstein L., Webster S. G., Miller S. C., Webster C. Plasticity of the differentiated state. Science. 1985 Nov 15;230(4727):758–766. doi: 10.1126/science.2414846. [DOI] [PubMed] [Google Scholar]
- Branch A. D., Benenfeld B. J., Robertson H. D. Ultraviolet light-induced crosslinking reveals a unique region of local tertiary structure in potato spindle tuber viroid and HeLa 5S RNA. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6590–6594. doi: 10.1073/pnas.82.19.6590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cole M. D. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361–384. doi: 10.1146/annurev.ge.20.120186.002045. [DOI] [PubMed] [Google Scholar]
- Crouch R. J., Kanaya S., Earl P. L. A model for the involvement of the small nucleolar RNA (U3) in processing eukaryotic ribosomal RNA. Mol Biol Rep. 1983 May;9(1-2):75–78. doi: 10.1007/BF00777476. [DOI] [PubMed] [Google Scholar]
- Cullen B. R., Hauber J., Campbell K., Sodroski J. G., Haseltine W. A., Rosen C. A. Subcellular localization of the human immunodeficiency virus trans-acting art gene product. J Virol. 1988 Jul;62(7):2498–2501. doi: 10.1128/jvi.62.7.2498-2501.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dani C., Blanchard J. M., Piechaczyk M., El Sabouty S., Marty L., Jeanteur P. Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046–7050. doi: 10.1073/pnas.81.22.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- DePinho R., Mitsock L., Hatton K., Ferrier P., Zimmerman K., Legouy E., Tesfaye A., Collum R., Yancopoulos G., Nisen P. Myc family of cellular oncogenes. J Cell Biochem. 1987 Apr;33(4):257–266. doi: 10.1002/jcb.240330404. [DOI] [PubMed] [Google Scholar]
- Enoch T., Zinn K., Maniatis T. Activation of the human beta-interferon gene requires an interferon-inducible factor. Mol Cell Biol. 1986 Mar;6(3):801–810. doi: 10.1128/mcb.6.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erba H. P., Gunning P., Kedes L. Nucleotide sequence of the human gamma cytoskeletal actin mRNA: anomalous evolution of vertebrate non-muscle actin genes. Nucleic Acids Res. 1986 Jul 11;14(13):5275–5294. doi: 10.1093/nar/14.13.5275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Felber B. K., Hadzopoulou-Cladaras M., Cladaras C., Copeland T., Pavlakis G. N. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495–1499. doi: 10.1073/pnas.86.5.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hadjiolov A. A., Nikolaev N. Maturation of ribosomal ribonucleic acids and the biogenesis of ribosomes. Prog Biophys Mol Biol. 1976;31(2):95–144. doi: 10.1016/0079-6107(78)90006-8. [DOI] [PubMed] [Google Scholar]
- Harders J., Lukács N., Robert-Nicoud M., Jovin T. M., Riesner D. Imaging of viroids in nuclei from tomato leaf tissue by in situ hybridization and confocal laser scanning microscopy. EMBO J. 1989 Dec 20;8(13):3941–3949. doi: 10.1002/j.1460-2075.1989.tb08577.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayashi S., Gillam I. C., Delaney A. D., Tener G. M. Acetylation of chromosome squashes of Drosophila melanogaster decreases the background in autoradiographs from hybridization with [125I]-labeled RNA. J Histochem Cytochem. 1978 Aug;26(8):677–679. doi: 10.1177/26.8.99471. [DOI] [PubMed] [Google Scholar]
- Henderson A. S., Eicher E. M., Yu M. T., Atwood K. C. The chromosomal location of ribosomal DNA in the mouse. Chromosoma. 1974;49(2):155–160. doi: 10.1007/BF00348887. [DOI] [PubMed] [Google Scholar]
- Henderson A. S., Warburton D., Atwood K. C. Location of ribosomal DNA in the human chromosome complement. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3394–3398. doi: 10.1073/pnas.69.11.3394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hidaka M., Inoue J., Yoshida M., Seiki M. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO J. 1988 Feb;7(2):519–523. doi: 10.1002/j.1460-2075.1988.tb02840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howell W. M., Black D. A. Controlled silver-staining of nucleolus organizer regions with a protective colloidal developer: a 1-step method. Experientia. 1980 Aug 15;36(8):1014–1015. doi: 10.1007/BF01953855. [DOI] [PubMed] [Google Scholar]
- Howell W. M., Denton T. E., Diamond J. R. Differential staining of the satellite regions of human acrocentric chromosomes. Experientia. 1975 Feb 15;31(2):260–262. doi: 10.1007/BF01990741. [DOI] [PubMed] [Google Scholar]
- Huber P. W., Wool I. G. Use of the cytotoxic nuclease alpha-sarcin to identify the binding site on eukaryotic 5 S ribosomal ribonucleic acid for the ribosomal protein L5. J Biol Chem. 1986 Mar 5;261(7):3002–3005. [PubMed] [Google Scholar]
- Huppi K., Duncan R., Potter M. Myc-1 is centromeric to the linkage group Ly-6--Sis--Gdc-1 on mouse chromosome 15. Immunogenetics. 1988;27(3):215–219. doi: 10.1007/BF00346589. [DOI] [PubMed] [Google Scholar]
- Inoue J., Yoshida M., Seiki M. Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653–3657. doi: 10.1073/pnas.84.11.3653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones T. R., Cole M. D. Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3' untranslated sequences. Mol Cell Biol. 1987 Dec;7(12):4513–4521. doi: 10.1128/mcb.7.12.4513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalland K. H., Langhoff E., Bos H. J., Göttlinger H., Haseltine W. A. Rex-dependent nucleolar accumulation of HTLV-I mRNAs. New Biol. 1991 Apr;3(4):389–397. [PubMed] [Google Scholar]
- Kanamori H., Suzuki N., Siomi H., Nosaka T., Sato A., Sabe H., Hatanaka M., Honjo T. HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA. EMBO J. 1990 Dec;9(12):4161–4166. doi: 10.1002/j.1460-2075.1990.tb07639.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keese P., Symons R. H. Domains in viroids: evidence of intermolecular RNA rearrangements and their contribution to viroid evolution. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4582–4586. doi: 10.1073/pnas.82.14.4582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
- Lawrence J. B., Singer R. H. Intracellular localization of messenger RNAs for cytoskeletal proteins. Cell. 1986 May 9;45(3):407–415. doi: 10.1016/0092-8674(86)90326-0. [DOI] [PubMed] [Google Scholar]
- Lawrence J. B., Singer R. H., Marselle L. M. Highly localized tracks of specific transcripts within interphase nuclei visualized by in situ hybridization. Cell. 1989 May 5;57(3):493–502. doi: 10.1016/0092-8674(89)90924-0. [DOI] [PubMed] [Google Scholar]
- Long E. O., Dawid I. B. Repeated genes in eukaryotes. Annu Rev Biochem. 1980;49:727–764. doi: 10.1146/annurev.bi.49.070180.003455. [DOI] [PubMed] [Google Scholar]
- Lüscher B., Eisenman R. N. c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock. Mol Cell Biol. 1988 Jun;8(6):2504–2512. doi: 10.1128/mcb.8.6.2504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malim M. H., Hauber J., Le S. Y., Maizel J. V., Cullen B. R. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254–257. doi: 10.1038/338254a0. [DOI] [PubMed] [Google Scholar]
- Miner J. H., Wold B. Herculin, a fourth member of the MyoD family of myogenic regulatory genes. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1089–1093. doi: 10.1073/pnas.87.3.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
- Nepveu A., Marcu K. B. Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO J. 1986 Nov;5(11):2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nigg E. A. Nuclear function and organization: the potential of immunochemical approaches. Int Rev Cytol. 1988;110:27–92. doi: 10.1016/s0074-7696(08)61847-1. [DOI] [PubMed] [Google Scholar]
- Potashkin J. A., Derby R. J., Spector D. L. Differential distribution of factors involved in pre-mRNA processing in the yeast cell nucleus. Mol Cell Biol. 1990 Jul;10(7):3524–3534. doi: 10.1128/mcb.10.7.3524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prestayko A. W., Tonato M., Busch H. Low molecular weight RNA associated with 28 s nucleolar RNA. J Mol Biol. 1970 Feb 14;47(3):505–515. doi: 10.1016/0022-2836(70)90318-9. [DOI] [PubMed] [Google Scholar]
- Ramsay G., Stanton L., Schwab M., Bishop J. M. Human proto-oncogene N-myc encodes nuclear proteins that bind DNA. Mol Cell Biol. 1986 Dec;6(12):4450–4457. doi: 10.1128/mcb.6.12.4450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rhodes S. J., Konieczny S. F. Identification of MRF4: a new member of the muscle regulatory factor gene family. Genes Dev. 1989 Dec;3(12B):2050–2061. doi: 10.1101/gad.3.12b.2050. [DOI] [PubMed] [Google Scholar]
- Rimsky L., Hauber J., Dukovich M., Malim M. H., Langlois A., Cullen B. R., Greene W. C. Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein. Nature. 1988 Oct 20;335(6192):738–740. doi: 10.1038/335738a0. [DOI] [PubMed] [Google Scholar]
- Schumacher J., Sänger H. L., Riesner D. Subcellular localization of viroids in highly purified nuclei from tomato leaf tissue. EMBO J. 1983;2(9):1549–1555. doi: 10.1002/j.1460-2075.1983.tb01622.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwab M., Varmus H. E., Bishop J. M., Grzeschik K. H., Naylor S. L., Sakaguchi A. Y., Brodeur G., Trent J. Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature. 1984 Mar 15;308(5956):288–291. doi: 10.1038/308288a0. [DOI] [PubMed] [Google Scholar]
- Siomi H., Shida H., Nam S. H., Nosaka T., Maki M., Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988 Oct 21;55(2):197–209. doi: 10.1016/0092-8674(88)90043-8. [DOI] [PubMed] [Google Scholar]
- Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22;321(6068):412–417. doi: 10.1038/321412a0. [DOI] [PubMed] [Google Scholar]
- Spector D. L., Ochs R. L., Busch H. Silver staining, immunofluorescence, and immunoelectron microscopic localization of nucleolar phosphoproteins B23 and C23. Chromosoma. 1984;90(2):139–148. doi: 10.1007/BF00292451. [DOI] [PubMed] [Google Scholar]
- Steitz J. A., Berg C., Hendrick J. P., La Branche-Chabot H., Metspalu A., Rinke J., Yario T. A 5S rRNA/L5 complex is a precursor to ribosome assembly in mammalian cells. J Cell Biol. 1988 Mar;106(3):545–556. doi: 10.1083/jcb.106.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stroke I. L., Weiner A. M. Genes and pseudogenes for rat U3A and U3B small nuclear RNA. J Mol Biol. 1985 Jul 20;184(2):183–193. doi: 10.1016/0022-2836(85)90372-9. [DOI] [PubMed] [Google Scholar]
- Tague B. W., Gerbi S. A. Processing of the large rRNA precursor: two proposed categories of RNA-RNA interactions in eukaryotes. J Mol Evol. 1984;20(3-4):362–367. doi: 10.1007/BF02104742. [DOI] [PubMed] [Google Scholar]
- Tapscott S. J., Davis R. L., Thayer M. J., Cheng P. F., Weintraub H., Lassar A. B. MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science. 1988 Oct 21;242(4877):405–411. doi: 10.1126/science.3175662. [DOI] [PubMed] [Google Scholar]
- Thayer M. J., Tapscott S. J., Davis R. L., Wright W. E., Lassar A. B., Weintraub H. Positive autoregulation of the myogenic determination gene MyoD1. Cell. 1989 Jul 28;58(2):241–248. doi: 10.1016/0092-8674(89)90838-6. [DOI] [PubMed] [Google Scholar]
- Thomas K., Del Mazo J., Eversole P., Bellvé A., Hiraoka Y., Li S. S., Simon M. Developmental regulation of expression of the lactate dehydrogenase (LDH) multigene family during mouse spermatogenesis. Development. 1990 Jun;109(2):483–493. doi: 10.1242/dev.109.2.483. [DOI] [PubMed] [Google Scholar]
- Urlaub G., Mitchell P. J., Ciudad C. J., Chasin L. A. Nonsense mutations in the dihydrofolate reductase gene affect RNA processing. Mol Cell Biol. 1989 Jul;9(7):2868–2880. doi: 10.1128/mcb.9.7.2868. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg R. A., Penman S. Small molecular weight monodisperse nuclear RNA. J Mol Biol. 1968 Dec;38(3):289–304. doi: 10.1016/0022-2836(68)90387-2. [DOI] [PubMed] [Google Scholar]
- White K. N., Nosaka T., Kanamori H., Hatanaka M., Honjo T. The nucleolar localisation signal of the HTLV-I protein p27rex is important for stabilisation of IL-2 receptor alpha subunit mRNA by p27rex. Biochem Biophys Res Commun. 1991 Feb 28;175(1):98–103. doi: 10.1016/s0006-291x(05)81205-7. [DOI] [PubMed] [Google Scholar]
- Zasloff M. tRNA transport from the nucleus in a eukaryotic cell: carrier-mediated translocation process. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6436–6440. doi: 10.1073/pnas.80.21.6436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- del Mazo J., Martín-Sempere M. J., Kremer L., Avila J. Centromere pattern in different mouse seminiferous tubule cells. Cytogenet Cell Genet. 1986;43(3-4):201–206. doi: 10.1159/000132321. [DOI] [PubMed] [Google Scholar]