Mol._Cell._Biol.-2006-Coldwell-8448-60.pdf (1.44 MB)
Specific isoforms of translation initiation factor 4GI show differences in translational activity
journal contribution
posted on 2023-06-08, 09:42 authored by Mark J Coldwell, Simon MorleyThe eukaryotic initiation factor (eIF) 4GI gene locus (eIF4GI) contains three identified promoters, generating alternately spliced mRNAs, yielding a total of five eIF4GI protein isoforms. Although eIF4GI plays a critical role in mRNA recruitment to the ribosomes, little is known about the functions of the different isoforms, their partner binding capacities, or the role of the homolog, eIF4GII, in translation initiation. To directly address this, we have used short interfering RNAs (siRNAs) expressed from DNA vectors to silence the expression of eIF4GI in HeLa cells. Here we show that reduced levels of specific mRNA and eIF4GI isoforms in HeLa cells promoted aberrant morphology and a partial inhibition of translation. The latter reflected dephosphorylation of 4E-BP1 and decreased eIF4F complex levels, with no change in eIF2 alpha phosphorylation. Expression of siRNA-resistant Myc-tagged eIF4GI isoforms has allowed us to show that the different isoforms exhibit significant differences in their ability to restore translation rates. Here we quantify the efficiency of eIF4GI promoter usage in mammalian cells and demonstrate that even though the longest isoform of eIF4GI (eIF4GIf) was relatively poorly expressed when reintroduced, it was more efficient at promoting the translation of cellular mRNAs than the more highly expressed shorter isoforms used in previous functional studies.
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Publication status
- Published
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- Published version
Journal
Molecular and Cellular BiologyISSN
0270-7306External DOI
Issue
22Volume
26Page range
8448-8460Pages
13.0Department affiliated with
- Biochemistry Publications
Notes
This is the first demonstration of functional differences between the isoforms of eIF4GI in mammalian cells. SM directed the research and was the corresponding author.Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2017-03-07Usage metrics
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