Global gene expression profiling reveals widespread yet distinctive translational responses to different eukaryotic translation initiation factor 2B-targeting stress pathways.
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.
Smirnova
Julia B
JB
Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Selley
Julian N
JN
Sanchez-Cabo
Fatima
F
Carroll
Kathleen
K
Eddy
A Alan
AA
McCarthy
John E G
JE
Hubbard
Simon J
SJ
Pavitt
Graham D
GD
Grant
Chris M
CM
Ashe
Mark P
MP
D000596:Amino Acids / Q000737:chemistry; D000440:Butanols / Q000633:toxicity; D003470:Culture Media / Q000737:chemistry; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D046228:Microarray Analysis; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012331:RNA, Fungal / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
D000596:Amino Acids; D000440:Butanols; D003470:Culture Media; D020717:Eukaryotic Initiation Factor-2B; D012331:RNA, Fungal; D012333:RNA, Messenger