LncRNAs of Saccharomyces cerevisiae dodge the cell cycle arrest imposed by the ethanol stress

Abstract

Ethanol impairs many subsystems of Saccharomyces cerevisiae, including the cell cycle. Cyclins and damage checkpoints drive the cell cycle. Two ethanol-responsive lncRNAs in yeast interact with cell cycle proteins, and here we investigated the role of these RNAs on the ethanol-stressed cell cycle. Our network dynamic modeling showed that the higher and lower ethanol tolerant strains undergo a cell cycle arrest during the ethanol stress. However, lower tolerant phenotype arrest in a later phase leading to its faster population rebound after the stress relief. Two lncRNAs can skip the arrests mentioned. The in silico overexpression of lnc9136 of SEY6210 (a lower tolerant strain), and CRISPR-Cas9 partial deletions of this lncRNA, evidenced that the one induces a regular cell cycle even under ethanol stress; this lncRNA binds to Gin4 and Hsl1, driving the Swe1p, Clb1/2, and cell cycle. Moreover, the lnc10883 of BY4742 (a higher tolerant strain) interacts to the Mec1p and represses Bub1p, circumventing the DNA and spindle damage checkpoints keeping a normal cell cycle even under DNA damage. Overall, we present the first evidence of the direct roles of lncRNAs on cell cycle proteins, the dynamics of this system in different ethanol tolerant phenotypes, and a new cell cycle model.