Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

Article


Rallis, C., Lopez-Maury, L., Georgescu, T., Pancaldi, V. and Bahler, J. 2014. Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth. Biology Open. 3 (2), pp. 161-171. https://doi.org/10.1242/bio.20147245
AuthorsRallis, C., Lopez-Maury, L., Georgescu, T., Pancaldi, V. and Bahler, J.
Abstract

Target of rapamycin complex 1 (TORC1), which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.

JournalBiology Open
Journal citation3 (2), pp. 161-171
ISSN2046-6390
Year2014
PublisherThe Company of Biologists Ltd
Publisher's version
License
CC BY
Digital Object Identifier (DOI)https://doi.org/10.1242/bio.20147245
Web address (URL)https://doi.org/10.1242/bio.20147245
Publication dates
Online24 Jan 2014
Publication process dates
Deposited13 Feb 2018
Accepted09 Dec 2013
Accepted09 Dec 2013
FunderBiotechnology and Biological Sciences Research Council
Wellcome Trust
LicenseCC BY 3.0
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