Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
In an attempt to elucidate the underlying longevity-promoting mechanisms of mutants lacking SCH9, which live three times as long as wild type chronologically, we measured their time-course gene expression profiles. We interpreted their expression time differences by statistical inferences based on prior biological knowledge, and identified the following significant changes: (i) between 12 and 24 h, stress response genes were up-regulated by larger fold changes and ribosomal RNA (rRNA) processing genes were down-regulated more dramatically; (ii) mitochondrial ribosomal protein genes were not up-regulated between 12 and 60 h as wild type were; (iii) electron transport, oxidative phosphorylation and TCA genes were down-regulated early; (iv) the up-regulation of TCA and electron transport was accompanied by deep down-regulation of rRNA processing over time; and (v) rRNA processing genes were more volatile over time, and three associated cis-regulatory elements [rRNA processing element (rRPE), polymerase A and C (PAC) and glucose response element (GRE)] were identified. Deletion of AZF1, which encodes the transcriptional factor that binds to the GRE element, reversed the lifespan extension of sch9Delta. The significant alterations in these time-dependent expression profiles imply that the lack of SCH9 turns on the longevity programme that extends the lifespan through changes in metabolic pathways and protection mechanisms, particularly, the regulation of aerobic respiration and rRNA processing.
Ge
Huanying
H
Andrus Gerontology Center, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Wei
Min
M
Fabrizio
Paola
P
Hu
Jia
J
Cheng
Chao
C
Longo
Valter D
VD
Li
Lei M
LM
D002952:Citric Acid Cycle / Q000235:genetics; D004579:Electron Transport / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000378:metabolism; D020218:Response Elements; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
C116478:AZF1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae