Open AccessGlobal Gene Expression Profiling Reveals Widespread yet Distinctive Translational Responses to Different Eukaryotic Translation Initiation Factor 2B-Targeting Stress Pathways
Author(s) -
Julia B. Smirnova,
J. Selley,
Fátima SánchezCabo,
Kathleen M. Carroll,
A. A. Eddy,
John E.G. McCarthy,
Simon J. Hubbard,
Graham D. Pavitt,
Chris M. Grant,
Mark P. Ashe
Publication year - 2005
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.25.21.9340-9349.2005
Subject(s) - biology , translational regulation , ribosome biogenesis , ribosome profiling , translation (biology) , microbiology and biotechnology , eukaryotic initiation factor , initiation factor , eif4ebp1 , gene expression , polysome , eif2 , integrated stress response , regulation of gene expression , gene , biogenesis , eif4a1 , protein biosynthesis , eukaryotic translation initiation factor 4 gamma , eukaryotic translation , genetics , messenger rna , ribosome , rna
Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeastGCN4 and mammalianATF4 ), 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.