Inhibition of TOR signalling in lea1 mutant induces apoptosis in Saccharomyces cerevisiae
- 27 Downloads
The target of rapamycin, TOR, maintains cell growth and proliferation under vivid environmental conditions by orchestrating wide array of growth-related process. In addition to environmental conditions, e.g., nutrient and stress, TOR also governs cellular response to varied intracellular cues including perturbed intracellular mRNA levels which may arise due to altered regulation of mRNA processing at splicing or turnover levels. The purpose of this study is to explore the role of TOR signalling in growth of cells with accumulated unprocessed RNA. Growth analysis of lea1∆ (splicing deficient) was carried out under varied conditions leading to nitrogen starvation. The expression of TORC1 and TORC2 marker genes was examined in this delete strain. Sensitivity of the lea1∆ towards oxidative agents was observed. Apoptosis was analyzed in caffeine-treated lea1∆ cells. The hypersensitivity of lea1∆ cells towards caffeine is outcome of highly perturbed TOR signalling. The growth defect is independent of PKC pathway. Cells with accumulated unprocessed RNA experience high oxidative stress that induces apoptosis. An inadequate TOR signalling in lea1∆ cells substantiates the effect of oxidative stress induced by accumulated RNA to the extent of inducing cell death via apoptosis.
KeywordsRNA accumulation Oxidative stress Reactive oxygen species Caffeine Splicing
Initial work contribution of Shubhi Sahni is highly acknowledged. We are highly thankful to Dr. Maria E. Cardenas for providing us Jk9-3d strain.
This study was designed by PK and RP. Experiments were performed by PK and analyzed along with VN, DK, AKM, and RP. PK and RP wrote the manuscript. PK completed all the figures. All the results and final version of manuscript were reviewed by all the authors.
This work was supported by research grant to RP from SERB, Department of Science and Technology, Govt. of India (grant no. SR/FT/LS-93/2010). Pavan is thankful to SERB for fellowship.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals (if applicable)
- Fadri M, Daquinag A, Wang S et al (2005) The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell 16:1883–1900. https://doi.org/10.1091/mbc.E04-07-0564 CrossRefPubMedPubMedCentralGoogle Scholar
- Kuranda K, Leberre V, Sokol S et al (2006) Investigating the caffeine effects in the yeast Saccharomyces cerevisiae brings new insights into the connection between TOR, PKC and Ras/cAMP signalling pathways. Mol Microbiol 61:1147–1166. https://doi.org/10.1111/j.1365-2958.2006.05300.x CrossRefPubMedGoogle Scholar
- Loewith R, Jacinto E, Wullschleger S et al (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. https://doi.org/10.1016/S1097-2765(02)00636-6
- Raju KK, Natarajan S, Kumar NS et al (2015) Role of cytoplasmic deadenylation and mRNA decay factors in yeast apoptosis. FEMS Yeast Res 15. https://doi.org/10.1093/femsyr/fou006
- Sariki SK, Sahu PK, Golla U et al (2016) Sen1, the homolog of human Senataxin, is critical for cell survival through regulation of redox homeostasis, mitochondrial function, and the TOR pathway in Saccharomyces cerevisiae. FEBS J 283:4056–4083. https://doi.org/10.1111/febs.13917 CrossRefPubMedGoogle Scholar