The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay.
The nonsense-mediated mRNA decay (NMD) pathway monitors premature translation termination and degrades aberrant mRNAs. In yeast, it has been proposed that a surveillance complex searches 3' of a nonsense codon for a downstream sequence element (DSE) associated with RNA-binding proteins. An interaction between the complex and the DSE-binding protein(s) triggers NMD. Here we describe the identification and characterization of the Hrp1/Nab4 protein as a DSE-binding factor that activates NMD. Mutations in HRP1 stabilize nonsense-containing transcripts without affecting the decay of wild-type mRNAs. Hrp1p binds specifically to a DSE-containing RNA and interacts with Upf1p, a component of the surveillance complex. A mutation in HRP1 that stabilizes nonsense-containing mRNAs abolishes its affinity for the DSE and fails to interact with Upf1p. We present a model describing how Hrp1p marks a transcript for rapid decay.
González
C I
CI
Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.
Ruiz-Echevarría
M J
MJ
Vasudevan
S
S
Henry
M F
MF
Peltz
S W
SW
D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D018389:Codon, Nonsense; D003593:Cytoplasm / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000378:metabolism; D020871:RNA Stability; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D020506:Untranslated Regions; D039221:mRNA Cleavage and Polyadenylation Factors
D018389:Codon, Nonsense; D005656:Fungal Proteins; C512636:HRP1 protein, S cerevisiae; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; D020506:Untranslated Regions; D039221:mRNA Cleavage and Polyadenylation Factors; D010735:Phosphoglycerate Kinase; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases