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Chemical genomics approach to identify genes associated with sensitivity to rapamycin in the fission yeast Schizosaccharomyces pombe
Author(s) -
Doi Akira,
Fujimoto Ayumi,
Sato Shun,
Uno Takaya,
Kanda Yuki,
Asami Keita,
Tanaka Yuriko,
Kita Ayako,
Satoh Ryosuke,
Sugiura Reiko
Publication year - 2015
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12223
Subject(s) - schizosaccharomyces pombe , biology , schizosaccharomyces , gene , genetics , yeast , ribosome biogenesis , chromatin , genome , calorie restriction , saccharomyces cerevisiae , computational biology , ribosome , rna , endocrinology
Rapamycin and its derivatives have now emerged as an attractive therapeutic strategy with both immunosuppressant and antitumor properties. In addition, rapamycin has been proposed as a calorie restriction mimetic to extend the life span of various organisms. The fission yeast S chizosaccharomyces pombe ( S . pombe ) serves as a valuable genetic model system to study the mechanism(s) of drug action as well as to determine genetic contexts associated with drug sensitivity or resistance. Here, we identified genes that when deleted modulate the rapamycin‐sensitive strains in S . pombe . We carried out a chemical genomics screen for rapamycin‐sensitive mutants using the genome‐deletion library which covers 95.3% of all nonessential fission yeast genes and confirmed 59 genes to be rapamycin sensitive. Gene Ontology (GO) enrichment analysis showed that strains sensitive to rapamycin are highly enriched in processes regulating t RNA modification and mitochondria as well as other ontologies, including cellular metabolic process, chromatin organization, cell cycle, signaling, translation, transport and other cellular processes. Analysis also showed that components of the Elongator complex are overrepresented in the sensitive strains. Here, the data obtained will provide valuable information for speculation on the actions of rapamycin as well as on TORC signaling, thereby presenting a strategy to enhance sensitivity to rapamycin.