PMID- 10357825 OWN - NLM STAT- MEDLINE DCOM- 19990805 LR - 20181113 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 18 IP - 11 DP - 1999 Jun 1 TI - Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA stability. PG - 3139-52 AB - 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. FAU - Vilela, C AU - Vilela C AD - Post-transcriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), PO Box 88, Manchester M60 1QD, UK. FAU - Ramirez, C V AU - Ramirez CV FAU - Linz, B AU - Linz B FAU - Rodrigues-Pousada, C AU - Rodrigues-Pousada C FAU - McCarthy, J E AU - McCarthy JE LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (5' Untranslated Regions) RN - 0 (CAD1 protein, S cerevisiae) RN - 0 (Codon, Initiator) RN - 0 (Codon, Terminator) RN - 0 (DNA-Binding Proteins) RN - 0 (Eukaryotic Initiation Factor-2) RN - 0 (Fungal Proteins) RN - 0 (RNA, Fungal) RN - 0 (RNA, Messenger) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Transcription Factors) RN - 0 (YAP1 protein, S cerevisiae) RN - EC 2.7.- (Protein Kinases) RN - EC 3.6.1.- (NAM7 protein, S cerevisiae) RN - EC 3.6.4.13 (RNA Helicases) SB - IM MH - 5' Untranslated Regions/chemistry/genetics/*metabolism MH - Base Sequence MH - Codon, Initiator/genetics MH - Codon, Terminator/genetics MH - DNA-Binding Proteins/genetics MH - Eukaryotic Initiation Factor-2/genetics/physiology MH - Fungal Proteins/genetics MH - Gene Expression Regulation, Fungal MH - Genes, Fungal/genetics/physiology MH - Half-Life MH - Models, Genetic MH - Mutation MH - Nucleic Acid Conformation MH - Open Reading Frames/genetics MH - Protein Biosynthesis/genetics MH - Protein Kinases/genetics MH - RNA Helicases/genetics/metabolism MH - RNA, Fungal/chemistry/genetics/metabolism MH - RNA, Messenger/chemistry/genetics/*metabolism MH - Ribosomes/*metabolism/physiology MH - Saccharomyces cerevisiae/*genetics/metabolism MH - *Saccharomyces cerevisiae Proteins MH - Transcription Factors/genetics PMC - PMC1171395 EDAT- 1999/06/05 00:00 MHDA- 1999/06/05 00:01 PMCR- 2000/06/01 CRDT- 1999/06/05 00:00 PHST- 1999/06/05 00:00 [pubmed] PHST- 1999/06/05 00:01 [medline] PHST- 1999/06/05 00:00 [entrez] PHST- 2000/06/01 00:00 [pmc-release] AID - 10.1093/emboj/18.11.3139 [doi] PST - ppublish SO - EMBO J. 1999 Jun 1;18(11):3139-52. doi: 10.1093/emboj/18.11.3139.