Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway
- PMID: 9032286
- PMCID: PMC231884
- DOI: 10.1128/MCB.17.3.1580
Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway
Abstract
Rapid turnover of nonsense-containing mRNAs in Saccharomyces cerevisiae is dependent on Upf1p, Nmd2p, and Upf3p, the products of the UPF1, NMD2/UPF2, and UPF3 genes, respectively. 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). In this study we have used the yeast two-hybrid system to define other protein-protein interactions among the essential components of this decay pathway. Nmd2p-Upf3p and Upf1p-Upf3p interactions were identified, and the respective domains involved in these interactions were delineated by deletion analysis. The domains of Upf1p and Upf3p putatively involved in their mutual interaction were found to correspond to the domains on the two proteins which interact with Nmd2p, suggesting that Nmd2p bridges Upf1p and Upf3p. This conclusion was reinforced by experiments showing that: (i) deletion of NMD2 completely abolishes interactions between Upf1p and Upf3p and (ii) overexpression of full-length Nmd2p or Nmd2p fragments that retain Upf1p- and Upf3p-interacting domains promotes 10- to 200-fold enhancement of Upf1p-Nmd2p-Upf3p complex formation. These results; the observation that cells harboring either single or multiple deletions of UPF1, NMD2, and UPF3 inhibit nonsense-mediated mRNA decay to the same extent; and an analysis of the possible targets of a dominant-negative NMD2 allele indicate that Upf1p, Nmd2p, Upf3p, and at least one other factor are functionally dependent, interacting components of the yeast nonsense-mediated mRNA decay pathway.
Similar articles
-
Transcript selection and the recruitment of mRNA decay factors for NMD in Saccharomyces cerevisiae.RNA. 2005 Sep;11(9):1333-9. doi: 10.1261/rna.2113605. Epub 2005 Jul 25. RNA. 2005. PMID: 16043493 Free PMC article. Review.
-
Interaction between Nmd2p and Upf1p is required for activity but not for dominant-negative inhibition of the nonsense-mediated mRNA decay pathway in yeast.RNA. 1996 Feb;2(2):153-70. RNA. 1996. PMID: 8601282 Free PMC article.
-
Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p.Mol Cell Biol. 2000 Jul;20(13):4591-603. doi: 10.1128/MCB.20.13.4591-4603.2000. Mol Cell Biol. 2000. PMID: 10848586 Free PMC article.
-
Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen.Genes Dev. 1995 Feb 15;9(4):437-54. doi: 10.1101/gad.9.4.437. Genes Dev. 1995. PMID: 7883168
-
NMD monitors translational fidelity 24/7.Curr Genet. 2017 Dec;63(6):1007-1010. doi: 10.1007/s00294-017-0709-4. Epub 2017 May 23. Curr Genet. 2017. PMID: 28536849 Free PMC article. Review.
Cited by
-
Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing.Mol Cell Biol. 2001 Nov;21(21):7366-79. doi: 10.1128/MCB.21.21.7366-7379.2001. Mol Cell Biol. 2001. PMID: 11585918 Free PMC article.
-
Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs.Mol Cell Biol. 2001 Mar;21(5):1515-30. doi: 10.1128/MCB.21.5.1515-1530.2001. Mol Cell Biol. 2001. PMID: 11238889 Free PMC article.
-
Transcript selection and the recruitment of mRNA decay factors for NMD in Saccharomyces cerevisiae.RNA. 2005 Sep;11(9):1333-9. doi: 10.1261/rna.2113605. Epub 2005 Jul 25. RNA. 2005. PMID: 16043493 Free PMC article. Review.
-
No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors.Biochem J. 2022 May 13;479(9):973-993. doi: 10.1042/BCJ20210556. Biochem J. 2022. PMID: 35551602 Free PMC article. Review.
-
Quality and quantity control of gene expression by nonsense-mediated mRNA decay.Nat Rev Mol Cell Biol. 2019 Jul;20(7):406-420. doi: 10.1038/s41580-019-0126-2. Nat Rev Mol Cell Biol. 2019. PMID: 30992545 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases