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Molecular and Cellular Biology, November 2006, p. 8448-8460, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01248-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Specific Isoforms of Translation Initiation Factor 4GI Show Differences in Translational Activity{triangledown} ,{dagger}

Mark J. Coldwell and Simon J. Morley*

Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom

Received 10 July 2006/ Returned for modification 1 August 2006/ Accepted 1 September 2006

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.

* Corresponding author. Mailing address: Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom. Phone: 44 (0) 1273 678544. Fax: 44 (0) 1273 678433. E-mail: s.j.morley{at}sussex.ac.uk.

{triangledown} Published ahead of print on 18 September 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, November 2006, p. 8448-8460, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01248-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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