Gonzalez CI, Ruiz-Echevarria MJ, Vasudevan S, Henry MF, Peltz SW

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

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