Chemical Strategies to Modulate and Manipulate RNA Epigenetic Modifications

作者：Liang Cheng · 发表于：Accounts of Chemical Research · 年份：2025 · DOI：10.1021/acs.accounts.4c00844 · 被引用次数：12 · 研究领域：RNA modifications and cancer、RNA Research and Splicing、RNA and protein synthesis mechanisms

Conspectus RNA epigenetics has rapidly emerged as a key frontier in chemical biology, revealing that modifications to RNA bases and riboses can fine-tune essential cellular processes such as gene expression, translation, and metabolic homeostasis. Traditionally, researchers have relied on manipulating the “writers,” “erasers,” and “readers” of RNA modifications─ i.e., protein cofactors─to alter and study these marks. Those enzyme-centric strategies, including small molecule inhibitors and CRISPR/Cas-based genetic perturbations, have been highly effective and are advancing in clinical applications. However, purely chemical approaches for installing, removing, or transforming RNA modifications without enzyme disturbance have offered distinct advantages, such as temporal control, reversibility, and bypassing compensatory biological feedback mechanisms that often arise with genetic or enzymatic inhibition. Every chemist should be concerned about RNA modifications, because they represent a striking intersection of molecular recognition, organic transformation, and cellular function. The ability to direct chemical reactivity at specific nucleosides in RNA can illuminate how individual modifications impact the overall gene regulation. Further, since improper RNA modification and damage patterns are implicated in cancer, metabolic disorders, and neurodegeneration, these chemical repair tools have potential as diagnostic and therapeutic interventions. Beyond medicine, agriculture also...