EIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs. Issue 13 (24th May 2017)

• Record Type: Journal Article
• Authors: Fijałkowska, Daria; Verbruggen, Steven; Ndah, Elvis; Jonckheere, Veronique; Menschaert, Gerben; Van Damme, Petra
• Is Part Of: Nucleic acids research. Volume 45:Issue 13(2017)
• Page Start: 7997
• Page End: 8013
• Publication Date: 2017-05-24
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx469
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Alternative translation initiation mechanisms such as leaky scanning and reinitiation potentiate the polycistronic nature of human transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stimuli. We combined proteomics with ribosome profiling and mRNA sequencing to identify the biological targets of translation control triggered by the eukaryotic translation initiation factor 1 (eIF1), a protein implicated in the stringency of start codon selection. We quantified expression changes of over 4000 proteins and 10 000 actively translated transcripts, leading to the identification of 245 transcripts undergoing translational control mediated by upstream open reading frames (uORFs) upon eIF1 deprivation. Here, the stringency of start codon selection and preference for an optimal nucleotide context were largely diminished leading to translational upregulation of uORFs with suboptimal start. Interestingly, genes affected by eIF1 deprivation were implicated in energy production and sensing of metabolic stress.