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

• Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p [4].
• This phenotype can be selected in crosses and is also seen in upf2 and upf3 mutants [5].
• Haploid cells lacking 82% of the IFS1 open reading frame are viable and phenotypically identical to ifs1-1 mutants [6].
• We provide evidence that the phosphorylation of the N-terminal region of Upf2p is crucial for its interaction with Hrp1p, an RNA-binding protein that we previously showed is essential for NMD [7].
• Upf1 and Upf2 proteins mediate normal yeast mRNA degradation when translation initiation is limited [8].

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

• Mutations in the cysteine- and histidine-rich region of Upf1p abolish Upf1p-Upf2p interaction [10].

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].

References