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 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.
Ruiz-Echevarría
M J
MJ
Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA. ruizeche@umdnj.edu
Peltz
S W
SW
D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics*; D039102:Poly(A)-Binding Proteins; D012331:RNA, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D005656:Fungal Proteins; C083327:PUB1 protein, S cerevisiae; D039102:Poly(A)-Binding Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins