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 Moriarty, P. M.
Right arrow Articles by Maquat, L. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moriarty, P. M.
Right arrow Articles by Maquat, L. E.

 Previous Article  |  Next Article 

Mol Cell Biol, May 1998, p. 2932-2939, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Selenium Deficiency Reduces the Abundance of mRNA for Se-Dependent Glutathione Peroxidase 1 by a UGA-Dependent Mechanism Likely To Be Nonsense Codon-Mediated Decay of Cytoplasmic mRNA

Patrick M. Moriarty,1 C. Channa Reddy,2 and Lynne E. Maquat1,*

Department of Human Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263,1 and Department of Veterinary Science, Pennsylvania State University, University Park, Pennsylvania 168022

Received 14 November 1997/Returned for modification 23 December 1997/Accepted 17 February 1998

The mammalian mRNA for selenium-dependent glutathione peroxidase 1 (Se-GPx1) contains a UGA codon that is recognized as a codon for the nonstandard amino acid selenocysteine (Sec). Inadequate concentrations of selenium (Se) result in a decrease in Se-GPx1 mRNA abundance by an uncharacterized mechanism that may be dependent on translation, independent of translation, or both. In this study, we have begun to elucidate this mechanism. We demonstrate using hepatocytes from rats fed either a Se-supplemented or Se-deficient diet for 9 to 13 weeks that Se deprivation results in an ~50-fold reduction in Se-GPx1 activity and an ~20-fold reduction in Se-GPx1 mRNA abundance. Reverse transcription-PCR analyses of nuclear and cytoplasmic fractions revealed that Se deprivation has no effect on the levels of either nuclear pre-mRNA or nuclear mRNA but reduces the level of cytoplasmic mRNA. The regulation of Se-GPx1 gene expression by Se was recapitulated in transient transfections of NIH 3T3 cells, and experiments were extended to examine the consequences of converting the Sec codon (TGA) to either a termination codon (TAA) or a cysteine codon (TGC). Regardless of the type of codon, an alteration in the Se concentration was of no consequence to the ratio of nuclear Se-GPx1 mRNA to nuclear Se-GPx1 pre-mRNA. The ratio of cytoplasmic Se-GPx1 mRNA to nuclear Se-GPx1 mRNA from the wild-type (TGA-containing) allele was reduced twofold when cells were deprived of Se for 48 h after transfection, which has been shown to be the extent of the reduction for the endogenous Se-GPx1 mRNA of cultured cells incubated as long as 20 days in Se-deficient medium. In contrast to the TGA allele, Se had no effect on expression of either the TAA allele or the TGC allele. Under Se-deficient conditions, the TAA and TGC alleles generated, respectively, 1.7-fold-less and 3-fold-more cytoplasmic Se-GPx1 mRNA relative to the amount of nuclear Se-GPx1 mRNA than the TGA allele. These results indicate that (i) under conditions of Se deprivation, the Sec codon reduces the abundance of cytoplasmic Se-GPx1 mRNA by a translation-dependent mechanism and (ii) there is no additional mechanism by which Se regulates Se-GPx1 mRNA production. These data suggest that the inefficient incorporation of Sec at the UGA codon during mRNA translation augments the nonsense-codon-mediated decay of cytoplasmic Se-GPx1 mRNA.

* Corresponding author. Mailing address: Department of Human Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: (716) 845-3325. Fax: (716) 845-8449. E-mail: Maquat{at}sc3101.med.buffalo.edu.

Mol Cell Biol, May 1998, p. 2932-2939, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Miranda, S. G., Wang, Y. J., Purdie, N. G., Osborne, V. R., Coomber, B. L., Cant, J. P. (2009). Selenomethionine stimulates expression of glutathione peroxidase 1 and 3 and growth of bovine mammary epithelial cells in primary culture. J DAIRY SCI 92: 2670-2683 [Abstract] [Full Text]  
  • Kobayashi, H., Matsuda, M., Fukuhara, A., Komuro, R., Shimomura, I. (2009). Dysregulated glutathione metabolism links to impaired insulin action in adipocytes. Am. J. Physiol. Endocrinol. Metab. 296: E1326-E1334 [Abstract] [Full Text]  
  • Zhou, J.-C., Zhao, H., Li, J.-G., Xia, X.-J., Wang, K.-N., Zhang, Y.-J., Liu, Y., Zhao, Y., Lei, X. G. (2009). Selenoprotein Gene Expression in Thyroid and Pituitary of Young Pigs Is Not Affected by Dietary Selenium Deficiency or Excess. J. Nutr. 139: 1061-1066 [Abstract] [Full Text]  
  • Barnes, K. M., Evenson, J. K., Raines, A. M., Sunde, R. A. (2009). Transcript Analysis of the Selenoproteome Indicates That Dietary Selenium Requirements of Rats Based on Selenium-Regulated Selenoprotein mRNA Levels Are Uniformly Less Than Those Based on Glutathione Peroxidase Activity. J. Nutr. 139: 199-206 [Abstract] [Full Text]  
  • Pagmantidis, V., Meplan, C., van Schothorst, E. M, Keijer, J., Hesketh, J. E (2008). Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes. Am. J. Clin. Nutr. 87: 181-189 [Abstract] [Full Text]  
  • Squires, J. E., Stoytchev, I., Forry, E. P., Berry, M. J. (2007). SBP2 Binding Affinity Is a Major Determinant in Differential Selenoprotein mRNA Translation and Sensitivity to Nonsense-Mediated Decay. Mol. Cell. Biol. 27: 7848-7855 [Abstract] [Full Text]  
  • Carlson, B. A., Moustafa, M. E., Sengupta, A., Schweizer, U., Shrimali, R., Rao, M., Zhong, N., Wang, S., Feigenbaum, L., Lee, B. J., Gladyshev, V. N., Hatfield, D. L. (2007). Selective Restoration of the Selenoprotein Population in a Mouse Hepatocyte Selenoproteinless Background with Different Mutant Selenocysteine tRNAs Lacking Um34. J. Biol. Chem. 282: 32591-32602 [Abstract] [Full Text]  
  • Durand, S., Cougot, N., Mahuteau-Betzer, F., Nguyen, C.-H., Grierson, D. S., Bertrand, E., Tazi, J., Lejeune, F. (2007). Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies. JCB 178: 1145-1160 [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]  
  • Hoffmann, P. R., Hoge, S. C., Li, P.-A., Hoffmann, F. W., Hashimoto, A. C., Berry, M. J. (2007). The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply. Nucleic Acids Res 35: 3963-3973 [Abstract] [Full Text]  
  • Jacobs, J. L., Belew, A. T., Rakauskaite, R., Dinman, J. D. (2007). Identification of functional, endogenous programmed -1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae. Nucleic Acids Res 35: 165-174 [Abstract] [Full Text]  
  • de Jesus, L. A., Hoffmann, P. R., Michaud, T., Forry, E. P., Small-Howard, A., Stillwell, R. J., Morozova, N., Harney, J. W., Berry, M. J. (2006). Nuclear Assembly of UGA Decoding Complexes on Selenoprotein mRNAs: a Mechanism for Eluding Nonsense-Mediated Decay?. Mol. Cell. Biol. 26: 1795-1805 [Abstract] [Full Text]  
  • Small-Howard, A., Morozova, N., Stoytcheva, Z., Forry, E. P., Mansell, J. B., Harney, J. W., Carlson, B. A., Xu, X.-m., Hatfield, D. L., Berry, M. J. (2006). Supramolecular complexes mediate selenocysteine incorporation in vivo.. Mol. Cell. Biol. 26: 2337-2346 [Abstract] [Full Text]  
  • Wittmann, J., Hol, E. M., Jack, H.-M. (2006). hUPF2 Silencing Identifies Physiologic Substrates of Mammalian Nonsense-Mediated mRNA Decay. Mol. Cell. Biol. 26: 1272-1287 [Abstract] [Full Text]  
  • Handy, D. E., Hang, G., Scolaro, J., Metes, N., Razaq, N., Yang, Y., Loscalzo, J. (2006). Aminoglycosides Decrease Glutathione Peroxidase-1 Activity by Interfering with Selenocysteine Incorporation. J. Biol. Chem. 281: 3382-3388 [Abstract] [Full Text]  
  • Kelly, V. P., Suzuki, T., Nakajima, O., Arai, T., Tamai, Y., Takahashi, S., Nishimura, S., Yamamoto, M. (2005). The Distal Sequence Element of the Selenocysteine tRNA Gene Is a Tissue-Dependent Enhancer Essential for Mouse Embryogenesis. Mol. Cell. Biol. 25: 3658-3669 [Abstract] [Full Text]  
  • Maquat, L. E. (2005). Nonsense-mediated mRNA decay in mammals. J. Cell Sci. 118: 1773-1776 [Full Text]  
  • Zhang, Y., Handy, D. E., Loscalzo, J. (2005). Adenosine-Dependent Induction of Glutathione Peroxidase 1 in Human Primary Endothelial Cells and Protection Against Oxidative Stress. Circ. Res. 96: 831-837 [Abstract] [Full Text]  
  • Handy, D. E., Zhang, Y., Loscalzo, J. (2005). Homocysteine Down-regulates Cellular Glutathione Peroxidase (GPx1) by Decreasing Translation. J. Biol. Chem. 280: 15518-15525 [Abstract] [Full Text]  
  • Carlson, B. A., Xu, X.-M., Gladyshev, V. N., Hatfield, D. L. (2005). Selective Rescue of Selenoprotein Expression in Mice Lacking a Highly Specialized Methyl Group in Selenocysteine tRNA. J. Biol. Chem. 280: 5542-5548 [Abstract] [Full Text]  
  • Mehta, A., Rebsch, C. M., Kinzy, S. A., Fletcher, J. E., Copeland, P. R. (2004). Efficiency of Mammalian Selenocysteine Incorporation. J. Biol. Chem. 279: 37852-37859 [Abstract] [Full Text]  
  • Bierl, C., Voetsch, B., Jin, R. C., Handy, D. E., Loscalzo, J. (2004). Determinants of Human Plasma Glutathione Peroxidase (GPx-3) Expression. J. Biol. Chem. 279: 26839-26845 [Abstract] [Full Text]  
  • Chiu, S.-Y., Lejeune, F., Ranganathan, A. C., Maquat, L. E. (2004). The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 18: 745-754 [Abstract] [Full Text]  
  • Wu, Y., Zhang, X., Bardag-Gorce, F., Robel, R. C. V., Aguilo, J., Chen, L., Zeng, Y., Hwang, K., French, S. W., Lu, S. C., Wan, Y.-J. Y. (2004). Retinoid X Receptor {alpha} Regulates Glutathione Homeostasis and Xenobiotic Detoxification Processes in Mouse Liver. Mol. Pharmacol. 65: 550-557 [Abstract] [Full Text]  
  • Throm, S. L., Klemsz, M. J. (2003). PU.1 regulates glutathione peroxidase expression in neutrophils. J. Leukoc. Biol. 74: 111-117 [Abstract] [Full Text]  
  • Maderazo, A. B., Belk, J. P., He, F., Jacobson, A. (2003). Nonsense-Containing mRNAs That Accumulate in the Absence of a Functional Nonsense-Mediated mRNA Decay Pathway Are Destabilized Rapidly upon Its Restitution. Mol. Cell. Biol. 23: 842-851 [Abstract] [Full Text]  
  • Forgione, M. A., Cap, A., Liao, R., Moldovan, N. I., Eberhardt, R. T., Lim, C. C., Jones, J., Goldschmidt-Clermont, P. J., Loscalzo, J. (2002). Heterozygous Cellular Glutathione Peroxidase Deficiency in the Mouse: Abnormalities in Vascular and Cardiac Function and Structure. Circulation 106: 1154-1158 [Abstract] [Full Text]  
  • Hatfield, D. L., Gladyshev, V. N. (2002). How Selenium Has Altered Our Understanding of the Genetic Code. Mol. Cell. Biol. 22: 3565-3576 [Full Text]  
  • Wang, J., Vock, V. M., Li, S., Olivas, O. R., Wilkinson, M. F. (2002). A Quality Control Pathway That Down-regulates Aberrant T-cell Receptor (TCR) Transcripts by a Mechanism Requiring UPF2 and Translation. J. Biol. Chem. 277: 18489-18493 [Abstract] [Full Text]  
  • Rao, L., Puschner, B., Prolla, T. A. (2001). Gene Expression Profiling of Low Selenium Status in the Mouse Intestine: Transcriptional Activation of Genes Linked to DNA Damage, Cell Cycle Control and Oxidative Stress. J. Nutr. 131: 3175-3181 [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]  
  • Rajavel, K. S., Neufeld, E. F. (2001). Nonsense-Mediated Decay of Human HEXA mRNA. Mol. Cell. Biol. 21: 5512-5519 [Abstract] [Full Text]  
  • Sun, X., Li, X., Moriarty, P. M., Henics, T., LaDuca, J. P., Maquat, L. E. (2001). Nonsense-mediated Decay of mRNA for the Selenoprotein Phospholipid Hydroperoxide Glutathione Peroxidase Is Detectable in Cultured Cells but Masked or Inhibited in Rat Tissues. Mol. Biol. Cell 12: 1009-1017 [Abstract] [Full Text]  
  • Copeland, P. R., Stepanik, V. A., Driscoll, D. M. (2001). Insight into Mammalian Selenocysteine Insertion: Domain Structure and Ribosome Binding Properties of Sec Insertion Sequence Binding Protein 2. Mol. Cell. Biol. 21: 1491-1498 [Abstract] [Full Text]  
  • Isshiki, M., Yamamoto, Y., Satoh, H., Shimamoto, K. (2001). Nonsense-Mediated Decay of Mutant waxy mRNA in Rice. Plant Physiol. 125: 1388-1395 [Abstract] [Full Text]  
  • Mitrovich, Q. M., Anderson, P. (2000). Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes Dev. 14: 2173-2184 [Abstract] [Full Text]  
  • Nasim, M. T., Jaenecke, S., Belduz, A., Kollmus, H., Flohe, L., McCarthy, J. E. G. (2000). Eukaryotic Selenocysteine Incorporation Follows a Nonprocessive Mechanism That Competes with Translational Termination. J. Biol. Chem. 275: 14846-14852 [Abstract] [Full Text]  
  • Wen, W., Weiss, S. L., Sunde, R. A. (1998). UGA Codon Position Affects the Efficiency of Selenocysteine Incorporation into Glutathione Peroxidase-1. J. Biol. Chem. 273: 28533-28541 [Abstract] [Full Text]  
  • Sun, X., Perlick, H. A., Dietz, H. C., Maquat, L. E. (1998). A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsensecontaining mRNAs in mammalian cells. Proc. Natl. Acad. Sci. USA 95: 10009-10014 [Abstract] [Full Text]  
  • Denning, G., Jamieson, L., Maquat, L. E., Thompson, E. A., Fields, A. P. (2001). Cloning of a Novel Phosphatidylinositol Kinase-related Kinase. CHARACTERIZATION OF THE HUMAN SMG-1 RNA SURVEILLANCE PROTEIN. J. Biol. Chem. 276: 22709-22714 [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»