Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae

Payne, Tom; Hanfrey, Colin; Bishop, Amy L.; Michael, Anthony J.; Avery, Simon V.; Archer, David B.

doi:10.1016/j.febslet.2008.01.009

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Volume 582, Issue 4 , Pages 503-509, 20 February 2008

Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae

Edited by Francesc Posas

Tom Payne
- School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
- Present address: Novozymes Biopharma U.K. Ltd., Castle Court, 59 Castle Boulevard, Nottingham NG7 1FD, UK.
Colin Hanfrey
- Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Amy L. Bishop
- School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
Anthony J. Michael
- Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Simon V. Avery
- School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
David B. Archer
- School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
- Corresponding author. Fax: +44 (0) 115 951 3251.

Received 15 November 2007; received in revised form 8 January 2008; accepted 10 January 2008. published online 17 January 2008.

Abstract

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR). Genome-wide analysis of translational regulation in response to the UPR-inducing agent dithiothreitol in Saccharomyces cerevisiae is reported. Microarray analysis, confirmed using qRT-PCR, identified transcript-specific translational regulation. Transcripts with functions in ribosomal biogenesis and assembly were translationally repressed. In contrast, mRNAs from known UPR genes, encoding the UPR transcription factor Hac1p, the ER-oxidoreductase Ero1p and the ER-associated protein degradation (ERAD) protein Der1p, were enriched in polysomal fractions, indicating translational up-regulation. Splicing of HAC1 mRNA is shown to be required for efficient ribosomal loading.

Keywords: Unfolded protein response, UPR, Stress, Microarray, Translation, Polysome, Saccharomyces