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Cell. 2000 Jun 23;101(7):741-51.

The RNA binding protein Pub1 modulates the stability of transcripts containing upstream open reading frames.

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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 functions to degrade transcripts containing nonsense codons. Transcripts containing mutations that insert an upstream open reading frame (uORF) in the 5'-UTR are degraded through NMD. However, several naturally occurring uORF-containing transcripts are resistant to NMD. Here we demonstrate that the GCN4 and YAP1 mRNAs, which contain uORFs, harbor a stabilizer element (STE) that prevents rapid NMD by interacting with the RNA binding protein Pub1. Conversely, a uORF-containing mRNA that lacks an STE, such as CPA1, is degraded by the NMD pathway. These results indicate that uORFs can play a pivotal role regulating both translation and turnover and that the Pub1p is a critical factor that modulates the stability of uORF-containing transcripts.

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