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Post‐termination ribosome interactions with the 5′UTR modulate yeast mRNA stability
Author(s) -
Vilela Cristina,
Ramirez Carmen Velasco,
Linz Bodo,
RodriguesPousada Claudina,
McCarthy John E.G.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.11.3139
Subject(s) - library science , biology , computer science
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.