title: Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA stability.
abstract: A novel form of post-transcriptional control is described. The 5' untranslated region (5'UTR) of the Saccharomyces cerevisiae gene encoding the AP1-like transcription factor Yap2 contains two upstream open reading frames (uORF1 and uORF2). The YAP2-type of uORF functions as a cis-acting element that attenuates gene expression at the level of mRNA turnover via termination-dependent decay. Release of post-termination ribosomes from the YAP2 5'UTR causes accelerated decay which is largely independent of the termination modulator gene UPF1. Both of the YAP2 uORFs contribute to the destabilization effect. A G/C-rich stop codon context, which seems to promote ribosome release, allows an uORF to act as a transferable 5'UTR-destabilizing element. Moreover, termination-dependent destabilization is potentiated by stable secondary structure 3' of the uORF stop codon. The potentiation of uORF-mediated destabilization is eliminated if the secondary structure is located further downstream of the uORF, and is also influenced by a modulatory mechanism involving eIF2. Destabilization is therefore linked to the kinetics of acquisition of reinitiation-competence by post-termination ribosomes in the 5'UTR. Our data explain the destabilizing properties of YAP2-type uORFs and also support a more general model for the mode of action of other known uORFs, such as those in the GCN4 mRNA.
authors.affiliation: Post-transcriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), PO Box 88, Manchester M60 1QD, UK.
authors.forename: C
authors.initials: C
authors.lastname: Vilela
authors.forename: C V
authors.initials: CV
authors.lastname: Ramirez
authors.forename: B
authors.initials: B
authors.lastname: Linz
authors.forename: C
authors.initials: C
authors.lastname: Rodrigues-Pousada
authors.forename: J E
authors.initials: JE
authors.lastname: McCarthy
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D006207:Half-Life; D008957:Models, Genetic; D009154:Mutation; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; C082904:CAD1 protein, S cerevisiae; D018387:Codon, Initiator; D018388:Codon, Terminator; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D005656:Fungal Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D011494:Protein Kinases; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases