This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Saltzman, A. L.
Right arrow Articles by Blencowe, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saltzman, A. L.
Right arrow Articles by Blencowe, B. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2008, p. 4320-4330, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.00361-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay {triangledown} ,{dagger}

Arneet L. Saltzman,1,2 Yoon Ki Kim,3,{ddagger} Qun Pan,2 Matthew M. Fagnani,1,2 Lynne E. Maquat,3 and Benjamin J. Blencowe1,2*

Department of Molecular Genetics,1 Banting and Best Department of Medical Research, Centre for Cellular and Biomolecular Research, 160 College Street, University of Toronto, Toronto, Ontario M5S 3E1, Canada,2 Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, New York 146423

Received 3 March 2008/ Returned for modification 1 April 2008/ Accepted 17 April 2008

Alternative splicing (AS) can regulate gene expression by introducing premature termination codons (PTCs) into spliced mRNA that subsequently elicit transcript degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the range of cellular functions controlled by this process and the factors required are poorly understood. By quantitative AS microarray profiling, we find that there are significant overlaps among the sets of PTC-introducing AS events affected by individual knockdown of the three core human NMD factors, Up-Frameshift 1 (UPF1), UPF2, and UPF3X/B. However, the levels of some PTC-containing splice variants are less or not detectably affected by the knockdown of UPF2 and/or UPF3X, compared with the knockdown of UPF1. The intron sequences flanking the affected alternative exons are often highly conserved, suggesting important regulatory roles for these AS events. The corresponding genes represent diverse cellular functions, and surprisingly, many encode core spliceosomal proteins and assembly factors. We further show that conserved, PTC-introducing AS events are enriched in genes that encode core spliceosomal proteins. Where tested, altering the expression levels of these core spliceosomal components affects the regulation of PTC-containing splice variants from the corresponding genes. Together, our results show that AS-coupled NMD can have different UPF factor requirements and is likely to regulate many general components of the spliceosome. The results further implicate general spliceosomal components in AS regulation.

* Corresponding author. Mailing address: University of Toronto, Donnelly CCBR, 160 College Street, Room 1016, Toronto, Ontario M5S 3E1, Canada. Phone: (416) 978-3016. Fax: (416) 978-5545. E-mail: b.blencowe{at}utoronto.ca

{triangledown} Published ahead of print on 28 April 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.

Molecular and Cellular Biology, July 2008, p. 4320-4330, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.00361-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Barberan-Soler, S., Lambert, N. J., Zahler, A. M. (2009). Global analysis of alternative splicing uncovers developmental regulation of nonsense-mediated decay in C. elegans. RNA 15: 1652-1660 [Abstract] [Full Text]  
  • Yamamoto, M. L., Clark, T. A., Gee, S. L., Kang, J.-A., Schweitzer, A. C., Wickrema, A., Conboy, J. G. (2009). Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis. Blood 113: 3363-3370 [Abstract] [Full Text]  
  • Rossbach, O., Hung, L.-H., Schreiner, S., Grishina, I., Heiner, M., Hui, J., Bindereif, A. (2009). Auto- and Cross-Regulation of the hnRNP L Proteins by Alternative Splicing. Mol. Cell. Biol. 29: 1442-1451 [Abstract] [Full Text]  
  • Sanford, J. R., Wang, X., Mort, M., VanDuyn, N., Cooper, D. N., Mooney, S. D., Edenberg, H. J., Liu, Y. (2009). Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Res 19: 381-394 [Abstract] [Full Text]  
  • Coles, J. L., Hallegger, M., Smith, C. W.J. (2009). A nonsense exon in the Tpm1 gene is silenced by hnRNP H and F. RNA 15: 33-43 [Abstract] [Full Text]  
  • Gong, C., Kim, Y. K., Woeller, C. F., Tang, Y., Maquat, L. E. (2009). SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs. Genes Dev. 23: 54-66 [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»