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 Gersappe, A.
Right arrow Articles by Pintel, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gersappe, A.
Right arrow Articles by Pintel, D. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 1999, p. 1640-1650, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Premature Termination Codon Interferes with the Nuclear Function of an Exon Splicing Enhancer in an Open Reading Frame-Dependent Manner

Anand Gersappe and David J. Pintel*

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri---Columbia, Columbia, Missouri 65212

Received 28 September 1998/Returned for modification 29 October 1998/Accepted 29 November 1998

Premature translation termination codon (PTC)-mediated effects on nuclear RNA processing have been shown to be associated with a number of human genetic diseases; however, how these PTCs mediate such effects in the nucleus is unclear. A PTC at nucleotide (nt) 2018 that lies adjacent to the 5' element of a bipartite exon splicing enhancer within the NS2-specific exon of minute virus of mice P4 promoter-generated pre-mRNA caused a decrease in the accumulated levels of P4-generated R2 mRNA relative to P4-generated R1 mRNA, although the total accumulated levels of P4 product remained the same. This effect was seen in nuclear RNA and was independent of RNA stability. The 5' and 3' elements of the bipartite NS2-specific exon enhancer are redundant in function, and when the 2018 PTC was combined with a deletion of the 3' enhancer element, the exon was skipped in the majority of the viral P4-generated product. Such exon skipping in response to a PTC, but not a missense mutation at nt 2018, could be suppressed by frame shift mutations in either exon of NS2 which reopened the NS2 open reading frame, as well as by improvement of the upstream intron 3' splice site. These results suggest that a PTC can interfere with the function of an exon splicing enhancer in an open reading frame-dependent manner and that the PTC is recognized in the nucleus.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri---Columbia, Columbia, MO 65212. Phone: (573) 882-3920. Fax: (573) 882-4287. E-mail: pinteld{at}missouri.edu.

Molecular and Cellular Biology, March 1999, p. 1640-1650, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lee, E.-G., Kuppers, D., Horn, M., Roy, J., May, C., Linial, M. L. (2008). A Premature Termination Codon Mutation at the C Terminus of Foamy Virus Gag Downregulates the Levels of Spliced pol mRNA. J. Virol. 82: 1656-1664 [Abstract] [Full Text]  
  • Chang, Y.-F., Chan, W.-K., Imam, J. S., Wilkinson, M. F. (2007). Alternatively Spliced T-cell Receptor Transcripts Are Up-regulated in Response to Disruption of Either Splicing Elements or Reading Frame. J. Biol. Chem. 282: 29738-29747 [Abstract] [Full Text]  
  • Isken, O., Maquat, L. E. (2007). Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev. 21: 1833-3856 [Abstract] [Full Text]  
  • BUHLER, M., MUHLEMANN, O. (2005). Alternative splicing induced by nonsense mutations in the immunoglobulin {micro} VDJ exon is independent of truncation of the open reading frame. RNA 11: 139-146 [Abstract] [Full Text]  
  • WACHTEL, C., LI, B., SPERLING, J., SPERLING, R. (2004). Stop codon-mediated suppression of splicing is a novel nuclear scanning mechanism not affected by elements of protein synthesis and NMD. RNA 10: 1740-1750 [Abstract] [Full Text]  
  • LYTLE, J. R., STEITZ, J. A. (2004). Premature termination codons do not affect the rate of splicing of neighboring introns. RNA 10: 657-668 [Abstract] [Full Text]  
  • Pagani, F., Buratti, E., Stuani, C., Baralle, F. E. (2003). Missense, Nonsense, and Neutral Mutations Define Juxtaposed Regulatory Elements of Splicing in Cystic Fibrosis Transmembrane Regulator Exon 9. J. Biol. Chem. 278: 26580-26588 [Abstract] [Full Text]  
  • Mendell, J. T., ap Rhys, C. M. J., Dietz, H. C. (2002). Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts. Science 298: 419-422 [Abstract] [Full Text]  
  • Maquat, L. E. (2002). NASty effects on fibrillin pre-mRNA splicing: another case of ESE does it, but proposals for translation-dependent splice site choice live on. Genes Dev. 16: 1743-1753 [Full Text]  
  • Wang, J., Hamilton, J. I., Carter, M. S., Li, S., Wilkinson, M. F. (2002). Alternatively Spliced TCR mRNA Induced by Disruption of Reading Frame. Science 297: 108-110 [Abstract] [Full Text]  
  • Wagner, E., Lykke-Andersen, J. (2002). mRNA surveillance: the perfect persist. J. Cell Sci. 115: 3033-3038 [Abstract] [Full Text]  
  • Kim, V. N., Kataoka, N., Dreyfuss, G. (2001). Role of the Nonsense-Mediated Decay Factor hUpf3 in the Splicing-Dependent Exon-Exon Junction Complex. Science 293: 1832-1836 [Abstract] [Full Text]  
  • Gersappe, A., Burger, L., Pintel, D. J. (1999). A Premature Termination Codon in Either Exon of Minute Virus of Mice P4 Promoter-generated Pre-mRNA Can Inhibit Nuclear Splicing of the Intervening Intron in an Open Reading Frame-dependent Manner. J. Biol. Chem. 274: 22452-22458 [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»