The RNA Binding Protein Pub1 Modulates the Stability of Transcripts Containing Upstream Open Reading Frames

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...

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Bibliographic Details
Published in:Cell 2000-06, Vol.101 (7), p.741-751
Main Authors: Ruiz-Echevarría, Maria J, Peltz, Stuart W
Format: Article
Language:English
Subjects:
5' Untranslated Regions - genetics
Base Sequence
Fungal Proteins - genetics
GCN4 gene
Gene Expression Regulation, Fungal
Molecular Sequence Data
Open Reading Frames - genetics
Poly(A)-Binding Proteins
Pub1 protein
RNA, Fungal - genetics
RNA, Messenger - genetics
RNA-binding protein
RNA-Binding Proteins - genetics
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription, Genetic
YAP1 gene
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80886-7