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Gene Review

NMD2  -  Nmd2p

Saccharomyces cerevisiae S288c

Synonyms: IFS1, Nonsense-mediated mRNA decay protein 2, SUA1, SUP111, UPF2, ...
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High impact information on NMD2

  • Upf1p is sufficient for targeting mRNAs to P-bodies, whereas Upf2p and Upf3p act, at least in part, downstream of P-body targeting to trigger decapping [1].
  • Our results demonstrate that the UPF2 gene encodes a putative 126.7-kD protein with an acidic region at its carboxyl terminus (-D-E)n found in many nucleolar and transcriptional activator proteins [2].
  • Mutation of the UPF2 gene or deletion of it from the chromosome resulted in stabilization of nonsense-containing mRNAs, whereas the decay of wild-type transcripts was not affected [2].
  • The UPF2 gene is dispensable for vegetative growth, but upf2 delta strains were found to be more sensitive to the translational elongation inhibitor cycloheximide than UPF2+ [2].
  • In this paper we report the identification and characterization of NMD2, a yeast gene that encodes a specific Upf1p-interacting protein [3].

Biological context of NMD2


Anatomical context of NMD2

  • Density gradient profiles for Upf1p were unchanged in the absence of Upf3p, and although similar, were modestly shifted to fractions lighter than those containing polyribosomes in the absence of Upf2p [9].

Associations of NMD2 with chemical compounds


Physical interactions of NMD2

  • We showed previously that Upf1p and Nmd2p interact and that this interaction is required for nonsense-mediated mRNA decay (F. He and A. Jacobson, Genes Dev. 9:437-454, 1995; F. He, A. H. Brown, and A. Jacobson, RNA 2:153-170, 1996) [11].

Regulatory relationships of NMD2

  • We also found that overexpression of Upf2p suppresses the Nmd(-) phenotype in mutant strains carrying nes-A alleles but has no effect on the localization of Upf3p [12].

Other interactions of NMD2

  • Our results indicate that Upf1p, Nmd2p, and Upf3p regulate decapping and exonucleolytic degradation of nonsense-containing mRNAs [13].
  • Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs [13].
  • Here we describe an improved method for isolating and readily distinguishing cis- from trans-acting suppressors of the upstream AUG. Eight different genes, designated sua1-sua8, are represented in our current collection of extragenic suppressors; all are recessive and enhance iso-1-cytochrome c levels to 10-60% of normal [14].


  1. Targeting of aberrant mRNAs to cytoplasmic processing bodies. Sheth, U., Parker, R. Cell (2006) [Pubmed]
  2. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Cui, Y., Hagan, K.W., Zhang, S., Peltz, S.W. Genes Dev. (1995) [Pubmed]
  3. Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen. He, F., Jacobson, A. Genes Dev. (1995) [Pubmed]
  4. Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p. Maderazo, A.B., He, F., Mangus, D.A., Jacobson, A. Mol. Cell. Biol. (2000) [Pubmed]
  5. Genetic background affects relative nonsense mRNA accumulation in wild-type and upf mutant yeast strains. Kebaara, B., Nazarenus, T., Taylor, R., Atkin, A.L. Curr. Genet. (2003) [Pubmed]
  6. A genetic screen identifies cellular factors involved in retroviral -1 frameshifting. Lee, S.I., Umen, J.G., Varmus, H.E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Role for Upf2p phosphorylation in Saccharomyces cerevisiae nonsense-mediated mRNA decay. Wang, W., Cajigas, I.J., Peltz, S.W., Wilkinson, M.F., González, C.I. Mol. Cell. Biol. (2006) [Pubmed]
  8. Upf1 and Upf2 proteins mediate normal yeast mRNA degradation when translation initiation is limited. Barnes, C.A. Nucleic Acids Res. (1998) [Pubmed]
  9. Relationship between yeast polyribosomes and Upf proteins required for nonsense mRNA decay. Atkin, A.L., Schenkman, L.R., Eastham, M., Dahlseid, J.N., Lelivelt, M.J., Culbertson, M.R. J. Biol. Chem. (1997) [Pubmed]
  10. Identification and characterization of mutations in the UPF1 gene that affect nonsense suppression and the formation of the Upf protein complex but not mRNA turnover. Weng, Y., Czaplinski, K., Peltz, S.W. Mol. Cell. Biol. (1996) [Pubmed]
  11. Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway. He, F., Brown, A.H., Jacobson, A. Mol. Cell. Biol. (1997) [Pubmed]
  12. Nuclear import of Upf3p is mediated by importin-alpha/-beta and export to the cytoplasm is required for a functional nonsense-mediated mRNA decay pathway in yeast. Shirley, R.L., Ford, A.S., Richards, M.R., Albertini, M., Culbertson, M.R. Genetics (2002) [Pubmed]
  13. Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs. He, F., Jacobson, A. Mol. Cell. Biol. (2001) [Pubmed]
  14. Extragenic suppressors of a translation initiation defect in the cyc1 gene of Saccharomyces cerevisiae. Hampsey, M., Na, J.G., Pinto, I., Ware, D.E., Berroteran, R.W. Biochimie (1991) [Pubmed]
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