This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buchman, A R Articles by Berg, P Search for Related Content PubMed PubMed Citation Articles by Buchman, A R Articles by Berg, P

 Previous Article  |  Next Article 

Mol Cell Biol. 1988 October; 8(10): 4395-4405

Comparison of intron-dependent and intron-independent gene expression.

Department of Biochemistry, Stanford University School of Medicine, California 94305.

ABSTRACT

Recombinant simian virus 40 viruses carrying rabbit beta-globin cDNA failed to express the beta-globin sequence unless an intron was included in the transcription unit. The addition of either beta-globin IVS1 or IVS2 caused a 400-fold increase in RNA production. Stable beta-globin RNA production required sequences in IVS2 that were very close to the splice sites and that coincided with those needed for mRNA splicing. In addition to the recombinant viruses, intron-dependent expression was observed with both replicating and nonreplicating plasmid vectors in short-term transfections of cultured animal cells. Unlike transcriptional enhancer elements, IVS2 failed to increase stable RNA production when it was placed downstream of the polyadenylation site. Using a plasmid vector system to survey different inserted sequences for their dependence on introns for expression, we found that the presence of IVS2 stimulated the expression of these sequences 2- to 500-fold. Sequences from the transcribed region of the herpes simplex virus thymidine kinase gene, a gene that lacks an intervening sequence, permitted substantial intron-independent expression (greater than 100-fold increase) in the plasmid vector system.

This article has been cited by other articles:

• Sridhar, S., Reyes-Sandoval, A., Draper, S. J., Moore, A. C., Gilbert, S. C., Gao, G. P., Wilson, J. M., Hill, A. V. S. (2008). Single-Dose Protection against Plasmodium berghei by a Simian Adenovirus Vector Using a Human Cytomegalovirus Promoter Containing Intron A. J. Virol. 82: 3822-3833 [Abstract] [Full Text]  
• Valencia, P., Dias, A. P., Reed, R. (2008). Splicing promotes rapid and efficient mRNA export in mammalian cells. Proc. Natl. Acad. Sci. USA 105: 3386-3391 [Abstract] [Full Text]  
• Rose, A. B., Elfersi, T., Parra, G., Korf, I. (2008). Promoter-Proximal Introns in Arabidopsis thaliana Are Enriched in Dispersed Signals that Elevate Gene Expression. Plant Cell 20: 543-551 [Abstract] [Full Text]  
• Bell, P., Vandenberghe, L. H., Wu, D., Johnston, J., Limberis, M., Wilson, J. M. (2007). A Comparative Analysis of Novel Fluorescent Proteins as Reporters for Gene Transfer Studies. J. Histochem. Cytochem. 55: 931-939 [Abstract] [Full Text]  
• Zhao, C., Hamilton, T. (2007). Introns Regulate the Rate of Unstable mRNA Decay. J. Biol. Chem. 282: 20230-20237 [Abstract] [Full Text]  
• Charron, M., Chern, J.-Y., Wright, W. W. (2007). The Cathepsin L First Intron Stimulates Gene Expression in Rat Sertoli Cells. Biol. Reprod. 76: 813-824 [Abstract] [Full Text]  
• Ali, H., LeRoy, G., Bridge, G., Flint, S. J. (2007). The Adenovirus L4 33-Kilodalton Protein Binds to Intragenic Sequences of the Major Late Promoter Required for Late Phase-Specific Stimulation of Transcription. J. Virol. 81: 1327-1338 [Abstract] [Full Text]  
• Silberstein, L., Sanchez, M.-J., Socolovsky, M., Liu, Y., Hoffman, G., Kinston, S., Piltz, S., Bowen, M., Gambardella, L., Green, A. R., Gottgens, B. (2005). Transgenic Analysis of the Stem Cell Leukemia +19 Stem Cell Enhancer in Adult and Embryonic Hematopoietic and Endothelial Cells. Stem Cells 23: 1378-1388 [Abstract] [Full Text]  
• Guang, S., Felthauser, A. M., Mertz, J. E. (2005). Binding of hnRNP L to the Pre-mRNA Processing Enhancer of the Herpes Simplex Virus Thymidine Kinase Gene Enhances both Polyadenylation and Nucleocytoplasmic Export of Intronless mRNAs. Mol. Cell. Biol. 25: 6303-6313 [Abstract] [Full Text]  
• Qiao, L., MacLean, P. S., Schaack, J., Orlicky, D. J., Darimont, C., Pagliassotti, M., Friedman, J. E., Shao, J. (2005). C/EBP{alpha} Regulates Human Adiponectin Gene Transcription Through an Intronic Enhancer. Diabetes 54: 1744-1754 [Abstract] [Full Text]  
• Nomura, M., Higuchi, T., Ishida, Y., Ohta, S., Komari, T., Imaizumi, N., Miyao-Tokutomi, M., Matsuoka, M., Tajima, S. (2005). Differential Expression Pattern of C4 Bundle Sheath Expression Genes in Rice, a C3 Plant. Plant Cell Physiol 46: 754-761 [Abstract] [Full Text]  
• Guang, S., Mertz, J. E. (2005). Pre-mRNA processing enhancer (PPE) elements from intronless genes play additional roles in mRNA biogenesis than do ones from intron-containing genes. Nucleic Acids Res 33: 2215-2226 [Abstract] [Full Text]  
• Bohne, J., Wodrich, H., Kräusslich, H.-G. (2005). Splicing of human immunodeficiency virus RNA is position-dependent suggesting sequential removal of introns from the 5' end. Nucleic Acids Res 33: 825-837 [Abstract] [Full Text]  
• Kahl, C. A., Marsh, J., Fyffe, J., Sanders, D. A., Cornetta, K. (2004). Human Immunodeficiency Virus Type 1-Derived Lentivirus Vectors Pseudotyped with Envelope Glycoproteins Derived from Ross River Virus and Semliki Forest Virus. J. Virol. 78: 1421-1430 [Abstract] [Full Text]  
• Xu, J., Gong, Z. Z. (2003). Intron requirement for AFP gene expression in Trichoderma viride. Microbiology 149: 3093-3097 [Abstract] [Full Text]  
• Wang, Q., Rymond, B. C. (2003). Rds3p Is Required for Stable U2 snRNP Recruitment to the Splicing Apparatus. Mol. Cell. Biol. 23: 7339-7349 [Abstract] [Full Text]  
• Noe, V., MacKenzie, S., Ciudad, C. J. (2003). An Intron Is Required for Dihydrofolate Reductase Protein Stability. J. Biol. Chem. 278: 38292-38300 [Abstract] [Full Text]  
• Wiegand, H. L., Lu, S., Cullen, B. R. (2003). Exon junction complexes mediate the enhancing effect of splicing on mRNA expression. Proc. Natl. Acad. Sci. USA 100: 11327-11332 [Abstract] [Full Text]  
• NOTT, A., MEISLIN, S. H., MOORE, M. J. (2003). A quantitative analysis of intron effects on mammalian gene expression. RNA 9: 607-617 [Abstract] [Full Text]  
• LU, S., CULLEN, B. R. (2003). Analysis of the stimulatory effect of splicing on mRNA production and utilization in mammalian cells. RNA 9: 618-630 [Abstract] [Full Text]  
• Winter, A. D., Myllyharju, J., Page, A. P. (2003). A Hypodermally Expressed Prolyl 4-Hydroxylase from the Filarial Nematode Brugia malayi Is Soluble and Active in the Absence of Protein Disulfide Isomerase. J. Biol. Chem. 278: 2554-2562 [Abstract] [Full Text]  
• Konetschny, C., Holzer, G. W., Falkner, F. G. (2002). Retroviral Vectors Produced in the Cytoplasmic Vaccinia Virus System Transduce Intron-Containing Genes. J. Virol. 76: 1236-1243 [Abstract] [Full Text]  
• Fuchs, F., Prokisch, H., Neupert, W., Westermann, B. (2002). Interaction of mitochondria with microtubules in the filamentous fungus Neurospora crassa. J. Cell Sci. 115: 1931-1937 [Abstract] [Full Text]  
• Zang, W.-Q., Li, B., Huang, P.-Y., Lai, M. M. C., Yen, T. S. B. (2001). Role of Polypyrimidine Tract Binding Protein in the Function of the Hepatitis B Virus Posttranscriptional Regulatory Element. J. Virol. 75: 10779-10786 [Abstract] [Full Text]  
• Moreau-Gaudry, F., Xia, P., Jiang, G., Perelman, N. P., Bauer, G., Ellis, J., Surinya, K. H., Mavilio, F., Shen, C.-K., Malik, P. (2001). High-level erythroid-specific gene expression in primary human and murine hematopoietic cells with self-inactivating lentiviral vectors. Blood 98: 2664-2672 [Abstract] [Full Text]  
• Wolfgang, M. J., Eisele, S. G., Browne, M. A., Schotzko, M. L., Garthwaite, M. A., Durning, M., Ramezani, A., Hawley, R. G., Thomson, J. A., Golos, T. G. (2001). Rhesus monkey placental transgene expression after lentiviral gene transfer into preimplantation embryos. Proc. Natl. Acad. Sci. USA 98: 10728-10732 [Abstract] [Full Text]  
• Turnage, M. A., Brewer-Jensen, P., Bai, W.-L., Searles, L. L. (2000). Arginine-Rich Regions Mediate the RNA Binding and Regulatory Activities of the Protein Encoded by the Drosophila melanogaster suppressor of sable Gene. Mol. Cell. Biol. 20: 8198-8208 [Abstract] [Full Text]  
• Ellison, K. S., Rice, S. A., Verity, R., Smiley, J. R. (2000). Processing of alpha -Globin and ICP0 mRNA in Cells Infected with Herpes Simplex Virus Type 1 ICP27 Mutants. J. Virol. 74: 7307-7319 [Abstract] [Full Text]  
• Szentirmay, M. N., Sawadogo, M. (2000). SURVEY AND SUMMARY: Spatial organization of RNA polymerase II transcription in the nucleus. Nucleic Acids Res 28: 2019-2025 [Abstract] [Full Text]  
• Cheung, P., Ellison, K. S., Verity, R., Smiley, J. R. (2000). Herpes Simplex Virus ICP27 Induces Cytoplasmic Accumulation of Unspliced Polyadenylated alpha -Globin Pre-mRNA in Infected HeLa Cells. J. Virol. 74: 2913-2919 [Abstract] [Full Text]  
• Ismail, S. I., Kingsman, S. M., Kingsman, A. J., Uden, M. (2000). Split-Intron Retroviral Vectors: Enhanced Expression with Improved Safety. J. Virol. 74: 2365-2371 [Abstract] [Full Text]  
• Rose, A. B., Beliakoff, J. A. (2000). Intron-Mediated Enhancement of Gene Expression Independent of Unique Intron Sequences and Splicing. Plant Physiol. 122: 535-542 [Abstract] [Full Text]  
• Luo, M.-j., Reed, R. (1999). From the Cover: Splicing is required for rapid and efficient mRNA export in metazoans. Proc. Natl. Acad. Sci. USA 96: 14937-14942 [Abstract] [Full Text]  
• Zhao, J., Hyman, L., Moore, C. (1999). Formation of mRNA 3' Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis. Microbiol. Mol. Biol. Rev. 63: 405-445 [Abstract] [Full Text]  
• Zufferey, R., Donello, J. E., Trono, D., Hope, T. J. (1999). Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances Expression of Transgenes Delivered by Retroviral Vectors. J. Virol. 73: 2886-2892 [Abstract] [Full Text]  
• Trubetskoy, A. M., Okenquist, S. A., Lenz, J. (1999). R Region Sequences in the Long Terminal Repeat of a Murine Retrovirus Specifically Increase Expression of Unspliced RNAs. J. Virol. 73: 3477-3483 [Abstract] [Full Text]  
• Otero, G. C., Hope, T. J. (1998). Splicing-Independent Expression of the Herpes Simplex Virus Type 1 Thymidine Kinase Gene Is Mediated by Three cis-Acting RNA Subelements. J. Virol. 72: 9889-9896 [Abstract] [Full Text]  
• Stutz, F., Rosbash, M. (1998). Nuclear RNA export. Genes Dev. 12: 3303-3319 [Full Text]  
• Li, K.-J., Garoff, H. (1998). Packaging of intron-containing genes into retrovirus vectors by alphavirus vectors. Proc. Natl. Acad. Sci. USA 95: 3650-3654 [Abstract] [Full Text]  
• Lai, W. S., Thompson, M. J., Blackshear, P. J. (1998). Characteristics of the Intron Involvement in the Mitogen-induced Expression of Zfp-36. J. Biol. Chem. 273: 506-517 [Abstract] [Full Text]  
• Huang, Y., Carmichael, G. G. (1997). The mouse histone H2a gene contains a small element that facilitates cytoplasmic accumulation of intronless gene transcripts and of unspliced HIV-1-related mRNAs. Proc. Natl. Acad. Sci. USA 94: 10104-10109 [Abstract] [Full Text]  
• Franco, P., Iaccarino, C., Chiaradonna, F., Brandazza, A., Iavarone, C., Mastronicola, M. R., Nolli, M. L., Stoppelli, M. P. (1997). Phosphorylation of Human Pro-Urokinase on Ser138/303 Impairs Its Receptor-dependent Ability to Promote Myelomonocytic Adherence and Motility. J. Cell Biol. 137: 779-791 [Abstract] [Full Text]  
• Huang, F., Gallo, V. (1997). Gene Structure of the Rat Kainate Receptor Subunit KA2 and Characterization of an Intronic Negative Regulatory Region. J. Biol. Chem. 272: 8618-8627 [Abstract] [Full Text]  
• Borradori, L., Koch, P. J., Niessen, C. M., Erkeland, S., Leusden, M. R. v., Sonnenberg, A. (1997). The Localization of Bullous Pemphigoid Antigen 180 (BP180) in Hemidesmosomes Is Mediated by Its Cytoplasmic Domain and Seems to be Regulated by the beta 4 Integrin Subunit. J. Cell Biol. 136: 1333-1347 [Abstract] [Full Text]  
• Nomura, M., Nawata, H., Morohashi, K.-i. (1996). Autoregulatory Loop in the Regulation of the Mammalian ftz-f1 Gene. J. Biol. Chem. 271: 8243-8249 [Abstract] [Full Text]  
• Liu, X, Mertz, J E (1995). HnRNP L binds a cis-acting RNA sequence element that enables intron-dependent gene expression.. Genes Dev. 9: 1766-1780 [Abstract]  
• Kurachi, S., Hitomi, Y., Furukawa, M., Kurachi, K. (1995). Role of Intron I in Expression of the Human Factor IX Gene. J. Biol. Chem. 270: 5276-5281 [Abstract] [Full Text]  
• Gherzi, R., Carnemolla, B., Siri, A., Ponassi, M., Balza, E., Zardi, L. (1995). Human Tenascin Gene. J. Biol. Chem. 270: 3429-3434 [Abstract] [Full Text]  
• Luehrsen, K R, Walbot, V (1994). Intron creation and polyadenylation in maize are directed by AU-rich RNA.. Genes Dev. 8: 1117-1130 [Abstract]  
• Lee, J, Jongeward, G D, Sternberg, P W (1994). unc-101, a gene required for many aspects of Caenorhabditis elegans development and behavior, encodes a clathrin-associated protein.. Genes Dev. 8: 60-73 [Abstract]  
• Wassarman, K M, Steitz, J A (1993). Association with terminal exons in pre-mRNAs: a new role for the U1 snRNP?. Genes Dev. 7: 647-659 [Abstract]  
• Niwa, M, Rose, S D, Berget, S M (1990). In vitro polyadenylation is stimulated by the presence of an upstream intron.. Genes Dev. 4: 1552-1559 [Abstract]  
• Clement, J. Q., Maiti, S., Wilkinson, M. F. (2001). Localization and Stability of Introns Spliced from the Pem Homeobox Gene. J. Biol. Chem. 276: 16919-16930 [Abstract] [Full Text]