The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay.

Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.
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.
Mesh Terms:
Biological Transport, Cell Nucleus, Codon, Nonsense, Cytoplasm, Fungal Proteins, Heterogeneous-Nuclear Ribonucleoproteins, Models, Genetic, Mutation, Nuclear Proteins, Phosphoglycerate Kinase, Protein Binding, Protein Biosynthesis, RNA Helicases, RNA Stability, RNA, Fungal, RNA, Messenger, RNA-Binding Proteins, Ribonucleoproteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Untranslated Regions, mRNA Cleavage and Polyadenylation Factors
Mol. Cell Mar. 01, 2000; 5(3);489-99 [PUBMED:10882134]
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