PMID:22156057

Citation	Loughran, G, Sachs, MS, Atkins, JF and Ivanov, IP (2012) Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5. Nucleic Acids Res. 40:2898-906
Abstract	An AUG in an optimal nucleotide context is the preferred translation initiation site in eukaryotic cells. Interactions among translation initiation factors, including eIF1 and eIF5, govern start codon selection. Experiments described here showed that high intracellular eIF5 levels reduced the stringency of start codon selection in human cells. In contrast, high intracellular eIF1 levels increased stringency. High levels of eIF5 induced translation of inhibitory upstream open reading frames (uORFs) in eIF5 mRNA that initiate with AUG codons in conserved poor contexts. This resulted in reduced translation from the downstream eIF5 start codon, indicating that eIF5 autoregulates its own synthesis. As with eIF1, which is also autoregulated through translation initiation, features contributing to eIF5 autoregulation show deep evolutionary conservation. The results obtained provide the basis for a model in which auto- and cross-regulation of eIF5 and eIF1 translation establish a regulatory feedback loop that would stabilize the stringency of start codon selection.
Links	PubMed PMC3326321 Online version:10.1093/nar/gkr1192
Keywords	Base Sequence; Codon, Initiator; Conserved Sequence; Eukaryotic Initiation Factor-1/metabolism; HEK293 Cells; Homeostasis; Humans; Peptide Chain Initiation, Translational; Peptide Initiation Factors/biosynthesis; Peptide Initiation Factors/genetics; Peptide Initiation Factors/metabolism; RNA, Messenger/chemistry; RNA-Binding Proteins/biosynthesis; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:EIF1		GO:0006446: regulation of translational initiation	ECO:0000314:		P		Fig 2-C,D Show that that over expression of EIF1 protein leads to decreased expression of firefly luciferase constructs downstream of a poor-context AUG start codons and other non-AUG start codons.	complete CACAO 3789
HUMAN:EIF1	involved_in	GO:0006446: regulation of translational initiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:IF5		GO:0006446: regulation of translational initiation	ECO:0000314:		P		Fig 2-C,D Show that that over expression of EIF5 protein leads to increased expression of firefly luciferase constructs downstream of a poor-context AUG start codons and other non-AUG start codons.	complete CACAO 3790
HUMAN:IF5	involved_in	GO:0006446: regulation of translational initiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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