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Molecular and Cellular Biology, November 2005, p. 9340-9349, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9340-9349.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Global Gene Expression Profiling Reveals Widespread yet Distinctive Translational Responses to Different Eukaryotic Translation Initiation Factor 2B-Targeting Stress Pathways{dagger}

Julia B. Smirnova,1 Julian N. Selley,2 Fatima Sanchez-Cabo,3 Kathleen Carroll,2 A. Alan Eddy,1 John E. G. McCarthy,2 Simon J. Hubbard,2 Graham D. Pavitt,1 Chris M. Grant,1 and Mark P. Ashe1*

Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Rd., Manchester, M13 9PT, United Kingdom,1 Faculty of Life Sciences, University of Manchester, The Mill, Sackville St., Manchester, M60 1QD, United Kingdom,2 Institute for Genomics and Bioinformatics, Christian Doppler Laboratory for Genomics and Bioinformatics, Graz University of Technology, 8010 Graz, Austria3

Received 27 May 2005/ Returned for modification 22 June 2005/ Accepted 1 August 2005

Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.

* Corresponding author. Mailing address: Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Rd., Manchester, M13 9PT, United Kingdom. Phone: 44 (0) 161 200 4164. Fax: 44 (0) 161 236 0409. E-mail: mark.p.ashe{at}manchester.ac.uk.

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

Molecular and Cellular Biology, November 2005, p. 9340-9349, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9340-9349.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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