Dataset Information

EIF1 modulates the recognition of sub-optimal translation start sites and steers gene expression control mediated by uORFs.

ABSTRACT: Alternative translation initiation mechanisms such as leaky scanning and re-initiation potentiate the polycistronic nature of transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stress 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 4,000 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. The stringency of start codon selection and preference for an optimal nucleotide context were largely diminished leading to translational upregulation of uORFs with sub-optimal start sites. Affected genes were implicated in energy production and sensing of metabolic stress. Interestingly, knockdown of eIF1 elicited a synergic response from eIF5 and eIF1B.

OTHER RELATED OMICS DATASETS IN: PRJNA344393

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Epithelial Cell, Colon

DISEASE(S): Colon Cancer,Acute Leukemia

SUBMITTER: Daria Gawron

LAB HEAD: Kris Gevaert

PROVIDER: PXD004980 | Pride | 2017-09-13

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	E11610_2p_5305b_HAP1_1A.raw	Raw
	E11612_2p_5305b_HAP1_1B.raw	Raw
	E11614_2p_5305b_HAP1_1C.raw	Raw
	E11622_2p_5305b_HAP1_3A.raw	Raw
	E11624_2p_5305b_HAP1_3B.raw	Raw

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Publications

eIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs.

Fijalkowska Daria D Verbruggen Steven S Ndah Elvis E Jonckheere Veronique V Menschaert Gerben G Van Damme Petra P

Nucleic acids research 20170701 13

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 selec ...[more]

PMID: 28541577

Similar Datasets

Project description:Translation of an mRNA in eukaryotes starts at AUG in most cases. Near-cognate codons (NCCs) such as UUG, ACG and AUU are also used as start sites at low levels in S. cerevisiae. Initiation from NCCs or AUGs in the 5’-untranslated regions (UTRs) of mRNAs can lead to translation of upstream open reading frames (uORFs) that might regulate expression of the main ORF (mORF). Although there is some circumstantial evidence that the translation of uORFs can be affected by environmental conditions, little is known about how it is affected by changes in growth temperature. Using reporter assays, we found that changes in growth temperature can affect translation from NCC start sites in yeast cells, suggesting the possibility that gene expression could be regulated by temperature by altering use of different uORF start codons. Using ribosome profiling, we provide evidence that growth temperature regulates the efficiency of translation of nearly 200 uORFs in S. cerevisiae. Of these uORFs, most that start with an AUG codon have increased translational efficiency at 37 ˚C relative to 30 ˚C and decreased efficiency at 20 ˚C. For translationally regulated uORFs starting with NCCs, we did not observe a general trend for the direction of regulation as a function of temperature, suggesting mRNA-specific features can determine the mode of temperature-dependent regulation. Consistent with this conclusion, the position of the uORFs in the 5’-leader relative to the 5’-cap and the start codon of the main ORF correlates with the direction of temperature-dependent regulation of uORF translation. We have identified several novel cases in which changes in uORF translation are inversely correlated with changes in the translational efficiency of the downstream main ORF. Our data suggest that translation of these mRNAs is subject to temperature-dependent, uORF-mediated regulation. Overall, our data suggest that alterations in the translation of specific uORFs by temperature can regulate gene expression in S. cerevisiae.