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Inhibition of TOR signalling in lea1 mutant induces apoptosis in Saccharomyces cerevisiae

  • Pavan Kumar
  • Debasree Kundu
  • Alok K. Mondal
  • Vikrant Nain
  • Rekha PuriaEmail author
Original Article
  • 27 Downloads

Abstract

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.

Keywords

RNA accumulation Oxidative stress Reactive oxygen species Caffeine Splicing 

Notes

Acknowledgements

Initial work contribution of Shubhi Sahni is highly acknowledged. We are highly thankful to Dr. Maria E. Cardenas for providing us Jk9-3d strain.

Author contribution

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.

Funding

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)

N/A

Informed consent

Yes

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Copyright information

© Università degli studi di Milano 2019

Authors and Affiliations

  • Pavan Kumar
    • 1
  • Debasree Kundu
    • 2
  • Alok K. Mondal
    • 2
  • Vikrant Nain
    • 1
  • Rekha Puria
    • 1
    Email author
  1. 1.School of BiotechnologyGautam Buddha UniversityGreater NoidaIndia
  2. 2.School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia

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