Post-termination ribosome interactions with the 5 ' UTR modulate yeast mRNA stability

A novel form of post-transcriptional control is described, The 5' untransla ted region (5'UTR) of the Saccharomyces cerevisiae gene encoding the AP1-li ke transcription factor Yap2 contains two upstream open reading frames (uOR F1 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-d ependent decay, Release of post-termination ribosomes from the YAP2 5'UTR c auses accelerated decay which is largely independent of the termination mod ulator gene UPF1, Both of the YAP2 uORFs contribute to the destabilization effect. A G/C-rich stop codon context, which seems to promote ribosome rele ase, allows an uORF to act as a transferable 5'UTR-destabilizing element, M oreover, termination-dependent destabilization is potentiated by stable sec ondary structure 3' of the uORF stop codon, The potentiation of uORF-mediat ed destabilization is eliminated if the secondary structure is located furt her downstream of the uORF, and is also influenced by a modulatory mechanis m involving eIF2, Destabilization is therefore linked to the kinetics of ac quisition 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 uOR Fs, such as those in the GCN4 mRNA.