Nucleic Acids Research Advance Access originally published online on October 30, 2009
Nucleic Acids Research 2010 38(1):143-158; doi:10.1093/nar/gkp849
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Nucleic Acids Research, 2010, Vol. 38, No. 1 143-158
© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Comparative analyses of time-course gene expression profiles of the long-lived sch9
mutant
1Molecular and Computational Biology, 2Andrus Gerontology Center, Department of Biological Sciences and 3Department of Mathematics, University of Southern California, Los Angeles, CA 90089, USA
*To whom correspondence should be addressed. Tel: 213 740 2407; Fax: 213 740 2437; Email: lilei{at}usc.edu
Received May 11, 2009. Revised September 19, 2009. Accepted September 23, 2009.
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 sch9
. 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.