Epitranscriptomics as a Candidate Universal Modulator of Dormancy Transitions

Dormancy has been widely recognized as an evolutionarily conserved strategy that enables cells and organisms to endure environmental stress, resource scarcity, or developmental arrest. While transcriptional regulation has been extensively studied in this context, increasing attention is being directed toward post-transcriptional mechanisms that allow rapid and energy-efficient control of gene expression. Among these, epitranscriptomic modifications, chemical marks added to RNA, have emerged as dynamic and reversible regulators of mRNA fate. In this perspective, it is proposed that RNA modifications can play a central role in establishing and maintaining dormancy across diverse biological systems. Evidence from plant seeds, microbial persisters, stem cells, and dormant cancer cells suggests that specific RNA marks, such as N6-methyladenosine (m⁶A), influence mRNA stability, translation, and localization in a context-dependent manner. It is argued that these modifications serve as a molecular interface between environmental signals and cellular responses, fine-tuning the transition between active and paused states. This article presents a unifying model, grounded in epitranscriptomics, in which RNA modifications modulate entry into, maintenance of, and exit from dormancy across taxa by tuning mRNA stability, translation, and localization-an underexplored regulatory layer in inactive states-and highlights key mechanistic insights, evolutionary parallels, and outstanding questions at the intersection of RNA regulation and cellular dormancy.