Abstract
Rodent BC1 RNA represents the first example of a neural cell-specific RNA polymerase III (Pol III) transcription product. By developing a rat brain in vitro system capable of supporting Pol III-directed transcription, we showed that the rat BC1 RNA intragenic promoter elements, comprising an A box element and a variant B box element, as well as its upstream region, containing octamer-binding consensus sequences and functional TATA and proximal sequence element sites, are necessary for transcription. The BC1 B box, lacking the invariant A residue found in the consensus B boxes of tRNAs, represents a functionally related and possibly distinct promoter element. The transcriptional activity of the BC1 B box element is greatly increased, in both a BC1 RNA and a chimeric tRNA(Leu) gene construct, when the BC1 5' flanking region is present and is appropriately spaced. Moreover, a tRNA consensus B-box sequence can efficiently replace the BC1 B box only if the BC1 upstream region is removed. These interactions, identified only in a homologous in vitro system, between upstream Pol II and intragenic Pol III promoters suggest a mechanism by which the tissue-specific BC1 RNA gene and possibly other Pol III-transcribed genes can be regulated.
Full Text
The Full Text of this article is available as a PDF (328.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bankier A. T., Weston K. M., Barrell B. G. Random cloning and sequencing by the M13/dideoxynucleotide chain termination method. Methods Enzymol. 1987;155:51–93. doi: 10.1016/0076-6879(87)55009-1. [DOI] [PubMed] [Google Scholar]
- Bieker J. J., Martin P. L., Roeder R. G. Formation of a rate-limiting intermediate in 5S RNA gene transcription. Cell. 1985 Jan;40(1):119–127. doi: 10.1016/0092-8674(85)90315-0. [DOI] [PubMed] [Google Scholar]
- Bogenhagen D. F., Sakonju S., Brown D. D. A control region in the center of the 5S RNA gene directs specific initiation of transcription: II. The 3' border of the region. Cell. 1980 Jan;19(1):27–35. doi: 10.1016/0092-8674(80)90385-2. [DOI] [PubMed] [Google Scholar]
- Brown D. D. How a simple animal gene works. Harvey Lect. 1980;76:27–44. [PubMed] [Google Scholar]
- Carbon P., Murgo S., Ebel J. P., Krol A., Tebb G., Mattaj L. W. A common octamer motif binding protein is involved in the transcription of U6 snRNA by RNA polymerase III and U2 snRNA by RNA polymerase II. Cell. 1987 Oct 9;51(1):71–79. doi: 10.1016/0092-8674(87)90011-0. [DOI] [PubMed] [Google Scholar]
- Ciliberto G., Castagnoli L., Cortese R. Transcription by RNA polymerase III. Curr Top Dev Biol. 1983;18:59–88. doi: 10.1016/s0070-2153(08)60579-7. [DOI] [PubMed] [Google Scholar]
- Clarkson S. G., Kurer V., Smith H. O. Sequence organization of a cloned tDNA met fragment from Xenopus laevis. Cell. 1978 Jul;14(3):713–724. doi: 10.1016/0092-8674(78)90253-2. [DOI] [PubMed] [Google Scholar]
- Comai L., Tanese N., Tjian R. The TATA-binding protein and associated factors are integral components of the RNA polymerase I transcription factor, SL1. Cell. 1992 Mar 6;68(5):965–976. doi: 10.1016/0092-8674(92)90039-f. [DOI] [PubMed] [Google Scholar]
- Das G., Henning D., Wright D., Reddy R. Upstream regulatory elements are necessary and sufficient for transcription of a U6 RNA gene by RNA polymerase III. EMBO J. 1988 Feb;7(2):503–512. doi: 10.1002/j.1460-2075.1988.tb02838.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeChiara T. M., Brosius J. Neural BC1 RNA: cDNA clones reveal nonrepetitive sequence content. Proc Natl Acad Sci U S A. 1987 May;84(9):2624–2628. doi: 10.1073/pnas.84.9.2624. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeFranco D., Schmidt O., Söll D. Two control regions for eukaryotic tRNA gene transcription. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3365–3368. doi: 10.1073/pnas.77.6.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dingermann T., Frank-Stoll U., Werner H., Wissmann A., Hillen W., Jacquet M., Marschalek R. RNA polymerase III catalysed transcription can be regulated in Saccharomyces cerevisiae by the bacterial tetracycline repressor-operator system. EMBO J. 1992 Apr;11(4):1487–1492. doi: 10.1002/j.1460-2075.1992.tb05193.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folk W. R. Changing directions in Pol III transcription. Genes Dev. 1988 Apr;2(4):373–375. doi: 10.1101/gad.2.4.373. [DOI] [PubMed] [Google Scholar]
- Fowlkes D. M., Shenk T. Transcriptional control regions of the adenovirus VAI RNA gene. Cell. 1980 Nov;22(2 Pt 2):405–413. doi: 10.1016/0092-8674(80)90351-7. [DOI] [PubMed] [Google Scholar]
- Gabrielsen O. S., Sentenac A. RNA polymerase III (C) and its transcription factors. Trends Biochem Sci. 1991 Nov;16(11):412–416. doi: 10.1016/0968-0004(91)90166-s. [DOI] [PubMed] [Google Scholar]
- Galli G., Hofstetter H., Birnstiel M. L. Two conserved sequence blocks within eukaryotic tRNA genes are major promoter elements. Nature. 1981 Dec 17;294(5842):626–631. doi: 10.1038/294626a0. [DOI] [PubMed] [Google Scholar]
- Geiduschek E. P., Tocchini-Valentini G. P. Transcription by RNA polymerase III. Annu Rev Biochem. 1988;57:873–914. doi: 10.1146/annurev.bi.57.070188.004301. [DOI] [PubMed] [Google Scholar]
- Gorski K., Carneiro M., Schibler U. Tissue-specific in vitro transcription from the mouse albumin promoter. Cell. 1986 Dec 5;47(5):767–776. doi: 10.1016/0092-8674(86)90519-2. [DOI] [PubMed] [Google Scholar]
- Hofstetter H., Kressman A., Birnstiel M. L. A split promoter for a eucaryotic tRNA gene. Cell. 1981 May;24(2):573–585. doi: 10.1016/0092-8674(81)90348-2. [DOI] [PubMed] [Google Scholar]
- Howe J. G., Shu M. D. Epstein-Barr virus small RNA (EBER) genes: unique transcription units that combine RNA polymerase II and III promoter elements. Cell. 1989 Jun 2;57(5):825–834. doi: 10.1016/0092-8674(89)90797-6. [DOI] [PubMed] [Google Scholar]
- Kim J., Martignetti J. A., Shen M. R., Brosius J., Deininger P. Rodent BC1 RNA gene as a master gene for ID element amplification. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3607–3611. doi: 10.1073/pnas.91.9.3607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kleinert H., Benecke B. J. Transcription of human 7S K DNA in vitro and in vivo is exclusively controlled by an upstream promoter. Nucleic Acids Res. 1988 Feb 25;16(4):1319–1331. doi: 10.1093/nar/16.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kressmann A., Hofstetter H., Di Capua E., Grosschedl R., Birnstiel M. L. A tRNA gene of Xenopus laevis contains at least two sites promoting transcription. Nucleic Acids Res. 1979 Dec 11;7(7):1749–1763. doi: 10.1093/nar/7.7.1749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunkel G. R., Pederson T. Upstream elements required for efficient transcription of a human U6 RNA gene resemble those of U1 and U2 genes even though a different polymerase is used. Genes Dev. 1988 Feb;2(2):196–204. doi: 10.1101/gad.2.2.196. [DOI] [PubMed] [Google Scholar]
- Kunkel G. R. RNA polymerase III transcription of genes that lack internal control regions. Biochim Biophys Acta. 1991 Jan 17;1088(1):1–9. doi: 10.1016/0167-4781(91)90146-d. [DOI] [PubMed] [Google Scholar]
- Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lassar A. B., Martin P. L., Roeder R. G. Transcription of class III genes: formation of preinitiation complexes. Science. 1983 Nov 18;222(4625):740–748. doi: 10.1126/science.6356356. [DOI] [PubMed] [Google Scholar]
- Lobo S. M., Hernandez N. A 7 bp mutation converts a human RNA polymerase II snRNA promoter into an RNA polymerase III promoter. Cell. 1989 Jul 14;58(1):55–67. doi: 10.1016/0092-8674(89)90402-9. [DOI] [PubMed] [Google Scholar]
- Lobo S. M., Lister J., Sullivan M. L., Hernandez N. The cloned RNA polymerase II transcription factor IID selects RNA polymerase III to transcribe the human U6 gene in vitro. Genes Dev. 1991 Aug;5(8):1477–1489. doi: 10.1101/gad.5.8.1477. [DOI] [PubMed] [Google Scholar]
- Makowski D. R., Haas R. A., Dolan K. P., Grunberger D. Molecular cloning, sequence analysis and in vitro expression of a rat tRNA gene cluster. Nucleic Acids Res. 1983 Dec 20;11(24):8609–8624. doi: 10.1093/nar/11.24.8609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manley J. L., Fire A., Cano A., Sharp P. A., Gefter M. L. DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855–3859. doi: 10.1073/pnas.77.7.3855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Margottin F., Dujardin G., Gérard M., Egly J. M., Huet J., Sentenac A. Participation of the TATA factor in transcription of the yeast U6 gene by RNA polymerase C. Science. 1991 Jan 25;251(4992):424–426. doi: 10.1126/science.1989075. [DOI] [PubMed] [Google Scholar]
- Martignetti J. A., Brosius J. BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11563–11567. doi: 10.1073/pnas.90.24.11563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martignetti J. A., Brosius J. Neural BC1 RNA as an evolutionary marker: guinea pig remains a rodent. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9698–9702. doi: 10.1073/pnas.90.20.9698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mattaj I. W., Dathan N. A., Parry H. D., Carbon P., Krol A. Changing the RNA polymerase specificity of U snRNA gene promoters. Cell. 1988 Nov 4;55(3):435–442. doi: 10.1016/0092-8674(88)90029-3. [DOI] [PubMed] [Google Scholar]
- McKinnon R. D., Shinnick T. M., Sutcliffe J. G. The neuronal identifier element is a cis-acting positive regulator of gene expression. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3751–3755. doi: 10.1073/pnas.83.11.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meza L., Araya A., Leon G., Krauskopf M. Specific alanine-tRNA species associated with fibroin biosynthesis in the posterior sild-gland of Bombyx mori L. FEBS Lett. 1977 May 15;77(2):255–260. doi: 10.1016/0014-5793(77)80246-9. [DOI] [PubMed] [Google Scholar]
- Murphy M. H., Baralle F. E. Directed semisynthetic point mutational analysis of an RNA polymerase III promoter. Nucleic Acids Res. 1983 Nov 25;11(22):7695–7700. doi: 10.1093/nar/11.22.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy S., Di Liegro C., Melli M. The in vitro transcription of the 7SK RNA gene by RNA polymerase III is dependent only on the presence of an upstream promoter. Cell. 1987 Oct 9;51(1):81–87. doi: 10.1016/0092-8674(87)90012-2. [DOI] [PubMed] [Google Scholar]
- Murphy S., Moorefield B., Pieler T. Common mechanisms of promoter recognition by RNA polymerases II and III. Trends Genet. 1989 Apr;5(4):122–126. doi: 10.1016/0168-9525(89)90043-7. [DOI] [PubMed] [Google Scholar]
- Murphy S., Pierani A., Scheidereit C., Melli M., Roeder R. G. Purified octamer binding transcription factors stimulate RNA polymerase III--mediated transcription of the 7SK RNA gene. Cell. 1989 Dec 22;59(6):1071–1080. doi: 10.1016/0092-8674(89)90763-0. [DOI] [PubMed] [Google Scholar]
- Nielsen J. N., Hallenberg C., Frederiksen S., Sørensen P. D., Lomholt B. Transcription of human 5S rRNA genes is influenced by an upstream DNA sequence. Nucleic Acids Res. 1993 Aug 11;21(16):3631–3636. doi: 10.1093/nar/21.16.3631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palmer J. M., Folk W. R. Unraveling the complexities of transcription by RNA polymerase III. Trends Biochem Sci. 1990 Aug;15(8):300–304. doi: 10.1016/0968-0004(90)90018-7. [DOI] [PubMed] [Google Scholar]
- Parry H. D., Mattaj I. W. Positive and negative functional interactions between promoter elements from different classes of RNA polymerase III-transcribed genes. EMBO J. 1990 Apr;9(4):1097–1104. doi: 10.1002/j.1460-2075.1990.tb08215.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakonju S., Bogenhagen D. F., Brown D. D. A control region in the center of the 5S RNA gene directs specific initiation of transcription: I. The 5' border of the region. Cell. 1980 Jan;19(1):13–25. doi: 10.1016/0092-8674(80)90384-0. [DOI] [PubMed] [Google Scholar]
- Schwartz L. B., Sklar V. E., Jaehning J. A., Weinmann R., Roeder R. G. Isolation and partial characterization of the multiple forms of deoxyribonucleic acid-dependent ribonucleic acid polymerase in the mouse myeloma, MOPC 315. J Biol Chem. 1974 Sep 25;249(18):5889–5897. [PubMed] [Google Scholar]
- Sharp P. A. TATA-binding protein is a classless factor. Cell. 1992 Mar 6;68(5):819–821. doi: 10.1016/0092-8674(92)90023-6. [DOI] [PubMed] [Google Scholar]
- Sharp S. J., Schaack J., Cooley L., Burke D. J., Söll D. Structure and transcription of eukaryotic tRNA genes. CRC Crit Rev Biochem. 1985;19(2):107–144. doi: 10.3109/10409238509082541. [DOI] [PubMed] [Google Scholar]
- Sharp S., DeFranco D., Dingermann T., Farrell P., Söll D. Internal control regions for transcription of eukaryotic tRNA genes. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6657–6661. doi: 10.1073/pnas.78.11.6657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simmen K. A., Bernués J., Parry H. D., Stunnenberg H. G., Berkenstam A., Cavallini B., Egly J. M., Mattaj I. W. TFIID is required for in vitro transcription of the human U6 gene by RNA polymerase III. EMBO J. 1991 Jul;10(7):1853–1862. doi: 10.1002/j.1460-2075.1991.tb07711.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sollner-Webb B. Surprises in polymerase III transcription. Cell. 1988 Jan 29;52(2):153–154. doi: 10.1016/0092-8674(88)90500-4. [DOI] [PubMed] [Google Scholar]
- Sprague K. U., Hagenbüchle O., Zuniga M. C. The nucleotide sequence of two silk gland alanine tRNAs: implications for fibroin synthesis and for initiator tRNA structure. Cell. 1977 Jul;11(3):561–570. doi: 10.1016/0092-8674(77)90074-5. [DOI] [PubMed] [Google Scholar]
- Sprague K. U., Larson D., Morton D. 5' flanking sequence signals are required for activity of silkworm alanine tRNA genes in homologous in vitro transcription systems. Cell. 1980 Nov;22(1 Pt 1):171–178. doi: 10.1016/0092-8674(80)90165-8. [DOI] [PubMed] [Google Scholar]
- Sugden B., Keller W. Mammalian deoxyribonucleic acid-dependent ribonucleic acid polymerases. I. Purification and properties of an -amanitin-sensitive ribonucleic acid polymerase and stimulatory factors from HeLa and KB cells. J Biol Chem. 1973 Jun 10;248(11):3777–3788. [PubMed] [Google Scholar]
- Sutcliffe J. G., Milner R. J., Gottesfeld J. M., Reynolds W. Control of neuronal gene expression. Science. 1984 Sep 21;225(4668):1308–1315. doi: 10.1126/science.6474179. [DOI] [PubMed] [Google Scholar]
- Tiedge H., Fremeau R. T., Jr, Weinstock P. H., Arancio O., Brosius J. Dendritic location of neural BC1 RNA. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2093–2097. doi: 10.1073/pnas.88.6.2093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Traboni C., Ciliberto G., Cortese R. Mutations in Box B of the promoter of a eucaryotic tRNAPro gene affect rate of transcription, processing, and stability of the transcripts. Cell. 1984 Jan;36(1):179–187. doi: 10.1016/0092-8674(84)90087-4. [DOI] [PubMed] [Google Scholar]
- Waibel F., Filipowicz W. RNA-polymerase specificity of transcription of Arabidopsis U snRNA genes determined by promoter element spacing. Nature. 1990 Jul 12;346(6280):199–202. doi: 10.1038/346199a0. [DOI] [PubMed] [Google Scholar]
- Watson J. B., Sutcliffe J. G. Primate brain-specific cytoplasmic transcript of the Alu repeat family. Mol Cell Biol. 1987 Sep;7(9):3324–3327. doi: 10.1128/mcb.7.9.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willis I. M. RNA polymerase III. Genes, factors and transcriptional specificity. Eur J Biochem. 1993 Feb 15;212(1):1–11. doi: 10.1111/j.1432-1033.1993.tb17626.x. [DOI] [PubMed] [Google Scholar]
- Wu G. J. Adenovirus DNA-directed transcription of 5.5S RNA in vitro. Proc Natl Acad Sci U S A. 1978 May;75(5):2175–2179. doi: 10.1073/pnas.75.5.2175. [DOI] [PMC free article] [PubMed] [Google Scholar]