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

Cell. 2000 Jun 23;101(7):741-51. doi: 10.1016/s0092-8674(00)80886-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions / genetics
  • Base Sequence
  • Fungal Proteins / genetics
  • Gene Expression Regulation, Fungal*
  • Molecular Sequence Data
  • Open Reading Frames / genetics*
  • Poly(A)-Binding Proteins*
  • RNA, Fungal / genetics
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*
  • Transcription, Genetic


  • 5' Untranslated Regions
  • Fungal Proteins
  • PUB1 protein, S cerevisiae
  • Poly(A)-Binding Proteins
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins