This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Coyle, J. H.
Right arrow Articles by Hammarskjöld, M.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coyle, J. H.
Right arrow Articles by Hammarskjöld, M.-L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2003, p. 92-103, Vol. 23, No. 1
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.1.92-103.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sam68 Enhances the Cytoplasmic Utilization of Intron-Containing RNA and Is Functionally Regulated by the Nuclear Kinase Sik/BRK

John H. Coyle,1 Brian W. Guzik,1 Yeou-Cherng Bor,1 Li Jin,1 Lucia Eisner-Smerage,1 Stephen J. Taylor,2 David Rekosh,1 and Marie-Louise Hammarskjöld1*

Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908,1 Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 947202

Received 6 June 2002/ Returned for modification 28 August 2002/ Accepted 20 September 2002

Cells normally restrict the nuclear export and expression of intron-containing mRNA. In many cell lines, this restriction can be overcome by inclusion of cis-acting elements, such as the Mason-Pfizer monkey virus constitutive transport element (CTE), in the RNA. In contrast, we observed that CTE-mediated expression from human immunodeficiency virus Gag-Pol reporters was very inefficient in 293 and 293T cells. However, addition of Sam68 led to a dramatic increase in the amount of Gag-Pol proteins produced in these cells. Enhancement of CTE function was not seen when a Sam68 point mutant (G178E) that is defective for RNA binding was used. Additionally, the effect of Sam68 was inhibited in a dose-dependent manner by coexpression of an activated form of the nuclear kinase Sik/BRK that hyperphosphorylated Sam68. RNA analysis showed that cytoplasmic Gag-Pol-CTE RNA levels were only slightly enhanced by the addition of Sam68, compared to a 60- to 70-fold increase in the levels of Gag-Pol protein expression. Thus, in this system, Sam68 functioned to enhance the cytoplasmic utilization of RNA containing the CTE. These results suggest that Sam68 may interact with specific RNAs in the nucleus to provide a "mark" that affects their cytoplasmic fate. They also provide further evidence of links between signal transduction and RNA utilization.

* Corresponding author. Mailing address: Myles H. Thaler Center for AIDS and Human Retrovirus Research and Department of Microbiology, University of Virginia, Charlottesville, VA 22908. Phone: (434) 982-1598. Fax: (434) 982-1590. E-mail: mh7g{at}virginia.edu.

Molecular and Cellular Biology, January 2003, p. 92-103, Vol. 23, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.1.92-103.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Groom, H. C. T., Anderson, E. C., Lever, A. M. L. (2009). Rev: beyond nuclear export. J. Gen. Virol. 90: 1303-1318 [Abstract] [Full Text]  
  • Paronetto, M. P., Messina, V., Bianchi, E., Barchi, M., Vogel, G., Moretti, C., Palombi, F., Stefanini, M., Geremia, R., Richard, S., Sette, C. (2009). Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. JCB 185: 235-249 [Abstract] [Full Text]  
  • Huot, M.-E., Brown, C. M., Lamarche-Vane, N., Richard, S. (2009). An Adaptor Role for Cytoplasmic Sam68 in Modulating Src Activity during Cell Polarization. Mol. Cell. Biol. 29: 1933-1943 [Abstract] [Full Text]  
  • Swartz, J. E., Bor, Y.-C., Misawa, Y., Rekosh, D., Hammarskjold, M.-L. (2007). The Shuttling SR Protein 9G8 Plays a Role in Translation of Unspliced mRNA Containing a Constitutive Transport Element. J. Biol. Chem. 282: 19844-19853 [Abstract] [Full Text]  
  • Ribet, D., Harper, F., Dewannieux, M., Pierron, G., Heidmann, T. (2007). Murine MusD Retrotransposon: Structure and Molecular Evolution of an "Intracellularized" Retrovirus. J. Virol. 81: 1888-1898 [Abstract] [Full Text]  
  • Caporale, M., Cousens, C., Centorame, P., Pinoni, C., De las Heras, M., Palmarini, M. (2006). Expression of the jaagsiekte sheep retrovirus envelope glycoprotein is sufficient to induce lung tumors in sheep.. J. Virol. 80: 8030-8037 [Abstract] [Full Text]  
  • Bor, Y., Swartz, J., Morrison, A., Rekosh, D., Ladomery, M., Hammarskjold, M.-L. (2006). The Wilms' tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron. Genes Dev. 20: 1597-1608 [Abstract] [Full Text]  
  • Paronetto, M. P., Zalfa, F., Botti, F., Geremia, R., Bagni, C., Sette, C. (2006). The Nuclear RNA-binding Protein Sam68 Translocates to the Cytoplasm and Associates with the Polysomes in Mouse Spermatocytes. Mol. Biol. Cell 17: 14-24 [Abstract] [Full Text]  
  • Lukong, K. E., Larocque, D., Tyner, A. L., Richard, S. (2005). Tyrosine Phosphorylation of Sam68 by Breast Tumor Kinase Regulates Intranuclear Localization and Cell Cycle Progression. J. Biol. Chem. 280: 38639-38647 [Abstract] [Full Text]  
  • Modem, S., Badri, K. R., Holland, T. C., Reddy, T. R. (2005). Sam68 is absolutely required for Rev function and HIV-1 production. Nucleic Acids Res 33: 873-879 [Abstract] [Full Text]  
  • Zhang, P., Ostrander, J. H., Faivre, E. J., Olsen, A., Fitzsimmons, D., Lange, C. A. (2005). Regulated Association of Protein Kinase B/Akt with Breast Tumor Kinase. J. Biol. Chem. 280: 1982-1991 [Abstract] [Full Text]  
  • Haegebarth, A., Heap, D., Bie, W., Derry, J. J., Richard, S., Tyner, A. L. (2004). The Nuclear Tyrosine Kinase BRK/Sik Phosphorylates and Inhibits the RNA-binding Activities of the Sam68-like Mammalian Proteins SLM-1 and SLM-2. J. Biol. Chem. 279: 54398-54404 [Abstract] [Full Text]  
  • RYDER, S. P., WILLIAMSON, J. R. (2004). Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination. RNA 10: 1449-1458 [Abstract] [Full Text]  
  • MCLAREN, M., ASAI, K., COCHRANE, A. (2004). A novel function for Sam68: Enhancement of HIV-1 RNA 3' end processing. RNA 10: 1119-1129 [Abstract] [Full Text]  
  • Fredj, N. B., Grange, J., Sadoul, R., Richard, S., Goldberg, Y., Boyer, V. (2004). Depolarization-induced translocation of the RNA-binding protein Sam68 to the dendrites of hippocampal neurons. J. Cell Sci. 117: 1079-1090 [Abstract] [Full Text]  
  • Sanchez-Velar, N., Udofia, E. B., Yu, Z., Zapp, M. L. (2004). hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region. Genes Dev. 18: 23-34 [Abstract] [Full Text]  
  • Jin, L., Guzik, B. W., Bor, Y.-c., Rekosh, D., Hammarskjold, M.-L. (2003). Tap and NXT promote translation of unspliced mRNA. Genes Dev. 17: 3075-3086 [Abstract] [Full Text]  
  • Roberts, T. M., Boris-Lawrie, K. (2003). Primary Sequence and Secondary Structure Motifs in Spleen Necrosis Virus RU5 Confer Translational Utilization of Unspliced Human Immunodeficiency Virus Type 1 Reporter RNA. J. Virol. 77: 11973-11984 [Abstract] [Full Text]  
  • Lasko, P. (2003). Gene Regulation at the RNA Layer: RNA Binding Proteins in Intercellular Signaling Networks. Sci Signal 2003: re6-re6 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»