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

@article{citeulike:1953979, 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.}, address = {Post-transcriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), PO Box 88, Manchester M60 1QD, UK.}, author = {Vilela, C. and Ramirez, C. V. and Linz, B. and Rodrigues-Pousada, C. and McCarthy, J. E. }, citeulike-article-id = {1953979}, issn = {0261-4189}, journal = {EMBO J}, keywords = {mrna, stability, utr}, month = {June}, number = {11}, pages = {3139--3152}, posted-at = {2007-11-21 19:59:41}, priority = {2}, title = {Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA stability.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10357825}, volume = {18}, year = {1999} }

TY - JOUR ID - citeulike:1953979 L3 - citeulike-article-id:1953979 TI - Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA stability. JF - EMBO J VL - 18 IS - 11 SP - 3139 EP - 3152 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. SN - 0261-4189 N2 - 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. KW - mrna KW - stability KW - utr AU - Vilela, C AU - Ramirez, CV AU - Linz, B AU - Rodrigues-Pousada, C AU - McCarthy, JE PY - 1999/06/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10357825 ER -