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 Maderazo, A. B.
Right arrow Articles by Jacobson, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maderazo, A. B.
Right arrow Articles by Jacobson, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2003, p. 842-851, Vol. 23, No. 3
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.3.842-851.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Nonsense-Containing mRNAs That Accumulate in the Absence of a Functional Nonsense-Mediated mRNA Decay Pathway Are Destabilized Rapidly upon Its Restitution

Alan B. Maderazo,{dagger} Jonathan P. Belk,2 Feng He, and Allan Jacobson*

Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0122

Received 29 July 2002/ Returned for modification 29 August 2002/ Accepted 25 October 2002

Nonsense-mediated mRNA decay (NMD) is a conserved proofreading mechanism that protects eukaryotic cells from the potentially deleterious effects of truncated proteins. Studies of Saccharomyces cerevisiae imply that NMD is a predominantly cytoplasmic decay pathway, while studies of mammalian systems suggest that decay of most substrate mRNAs may occur while they are still associated with the nucleus, possibly during a round of translation that occurs during their export to the cytoplasm. Complete entry of the latter mRNAs into the cytoplasm appears to render them immune to further NMD; i.e., they escape further susceptibility to this decay pathway. To determine if yeast cytoplasmic nonsense-containing mRNAs that evade decay are subsequently immune to NMD, we examined the consequences of placing each of the three UPF/NMD genes under the control of a galactose-inducible promoter. The decay kinetics of ADE2 and PGK1 nonsense-containing mRNAs were then analyzed when expression of UPF1, NMD2, or UPF3 was either repressed or subsequently induced. Results from these experiments demonstrated that activation of NMD caused rapid and immediate degradation of both substrate transcripts, with half-lives of both stable mRNA populations shortened to approximately 7 min. These findings make it unlikely that yeast nonsense-containing mRNAs can escape degradation by NMD and indicate that such mRNAs are available to this decay pathway at each round of translation.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave. N., Worcester, MA 01655-0122. Phone: (508) 856-2442. Fax: (508) 856-5920. E-mail: Allan.Jacobson{at}umassmed.edu.

{dagger} Present address: Gen-Probe Inc., San Diego, CA 92121-4362.

{ddagger} Present address: Department of HuMAbs, Bioresearch Center, Worcester, MA 01605-4314.

Molecular and Cellular Biology, February 2003, p. 842-851, Vol. 23, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.3.842-851.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zheng, W., Finkel, J. S., Landers, S. M., Long, R. M., Culbertson, M. R. (2008). Nonsense-Mediated Decay of ash1 Nonsense Transcripts in Saccharomyces cerevisiae. Genetics 180: 1391-1405 [Abstract] [Full Text]  
  • Takahashi, S., Araki, Y., Ohya, Y., Sakuno, T., Hoshino, S.-I., Kontani, K., Nishina, H., Katada, T. (2008). Upf1 potentially serves as a RING-related E3 ubiquitin ligase via its association with Upf3 in yeast. RNA 14: 1950-1958 [Abstract] [Full Text]  
  • Johansson, M. J. O., He, F., Spatrick, P., Li, C., Jacobson, A. (2007). Association of yeast Upf1p with direct substrates of the NMD pathway. Proc. Natl. Acad. Sci. USA 104: 20872-20877 [Abstract] [Full Text]  
  • Luke, B., Azzalin, C. M., Hug, N., Deplazes, A., Peter, M., Lingner, J. (2007). Saccharomyces cerevisiae Ebs1p is a putative ortholog of human Smg7 and promotes nonsense-mediated mRNA decay. Nucleic Acids Res 35: 7688-7697 [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]  
  • Morozov, I. Y., Negrete-Urtasun, S., Tilburn, J., Jansen, C. A., Caddick, M. X., Arst, H. N. Jr. (2006). Nonsense-Mediated mRNA Decay Mutation in Aspergillus nidulans. Eukaryot Cell 5: 1838-1846 [Abstract] [Full Text]  
  • WEIL, J. E., BEEMON, K. L. (2006). A 3' UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus. RNA 12: 102-110 [Abstract] [Full Text]  
  • CULBERTSON, M. R., NEENO-ECKWALL, E. (2005). Transcript selection and the recruitment of mRNA decay factors for NMD in Saccharomyces cerevisiae. RNA 11: 1333-1339 [Abstract] [Full Text]  
  • Gao, Q., Das, B., Sherman, F., Maquat, L. E. (2005). Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast. Proc. Natl. Acad. Sci. USA 102: 4258-4263 [Abstract] [Full Text]  
  • KUPERWASSER, N., BROGNA, S., DOWER, K., ROSBASH, M. (2004). Nonsense-mediated decay does not occur within the yeast nucleus. RNA 10: 1907-1915 [Abstract] [Full Text]  
  • KEELING, K. M., LANIER, J., DU, M., SALAS-MARCO, J., GAO, L., KAENJAK-ANGELETTI, A., BEDWELL, D. M. (2004). Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae. RNA 10: 691-703 [Abstract] [Full Text]  
  • Plant, E. P., Wang, P., Jacobs, J. L., Dinman, J. D. (2004). A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element. Nucleic Acids Res 32: 784-790 [Abstract] [Full Text]  
  • Das, B., Butler, J. S., Sherman, F. (2003). Degradation of Normal mRNA in the Nucleus of Saccharomyces cerevisiae. Mol. Cell. Biol. 23: 5502-5515 [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»