Specific isoforms of translation initiation factor 4GI show differences in translational activity

Coldwell, Mark J and Morley, Simon J (2006) Specific isoforms of translation initiation factor 4GI show differences in translational activity. Molecular and Cellular Biology, 26 (22). pp. 8448-8460. ISSN 0270-7306

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The 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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Simon Morley
Date Deposited: 06 Feb 2012 21:20
Last Modified: 07 Aug 2019 10:56
URI: http://sro.sussex.ac.uk/id/eprint/30815

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