RNA-Seq data - "Thiolutin Extends Replicative Lifespan by Rewiring Yeast Transcription and Metabolism"

Abstract

Transcription is a fundamental process that underlies gene expression and protein synthesis, with RNA polymerases serving as central regulators of cellular activity. Inhibition of RNA polymerases I, II, and III provides valuable insights into the coordination of gene expression, energy metabolism, and genome maintenance, and holds considerable therapeutic potential. Thiolutin, a well-established transcriptional inhibitor in yeast, remains an essential tool for probing the dynamics of RNA synthesis and global transcriptional control. Beyond its canonical role, thiolutin reduces intracellular ATP levels underscoring its multifaceted impact on metabolism. Here, we report for the first time that thiolutin markedly enhances the reproductive capacity of mitotically active yeast cells, thereby extending their replicative lifespan. In contrast, thiolutin accelerates chronological aging, revealing a striking divergence between replicative and chronological longevity. Moreover, thiolutin-mediated inhibition of RNA polymerases alters the expression of more than 60% of annotated genes, as demonstrated by RNA-Seq analysis, and profoundly reshapes the biochemical fingerprint of the cell as detected by Raman spectroscopy.