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- W2102050179 abstract "Eukaryotic cells rapidly reduce protein synthesis in response to various stress conditions. This can be achieved by the phosphorylation-mediated inactivation of a key translation initiation factor, eukaryotic initiation factor 2 (eIF2). However, the persistent translation of certain mRNAs is required for deployment of an adequate stress response. We carried out ribosome profiling of cultured human cells under conditions of severe stress induced with sodium arsenite. Although this led to a 5.4-fold general translational repression, the protein coding open reading frames (ORFs) of certain individual mRNAs exhibited resistance to the inhibition. Nearly all resistant transcripts possess at least one efficiently translated upstream open reading frame (uORF) that represses translation of the main coding ORF under normal conditions. Site-specific mutagenesis of two identified stress resistant mRNAs (PPP1R15B and IFRD1) demonstrated that a single uORF is sufficient for eIF2-mediated translation control in both cases. Phylogenetic analysis suggests that at least two regulatory uORFs (namely, in SLC35A4 and MIEF1) encode functional protein products." @default.
- W2102050179 created "2016-06-24" @default.
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- W2102050179 date "2015-01-26" @default.
- W2102050179 modified "2023-10-14" @default.
- W2102050179 title "Translation of 5′ leaders is pervasive in genes resistant to eIF2 repression" @default.
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- W2102050179 doi "https://doi.org/10.7554/elife.03971" @default.
- W2102050179 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4383229" @default.
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- W2102050179 hasPublicationYear "2015" @default.
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