RNA Aptamers and Epitranscriptomics: Charting Unexplored Territories in RNA Biology

The fields of RNA aptamers and epitranscriptomics have each emerged as powerful dimensions of RNA biology, yet their conceptual and mechanistic overlap remains largely unexplored. RNA aptamers as in vitro-selected single-stranded RNA oligonucleotides selected through in vitro evolution (Systematic Evolution of Ligands by Exponential Enrichment [SELEX]) and related methods are well known for their ability to fold into precise three-dimensional structures and bind specific targets with high affinity. These aptamers have been widely used in diagnostics, therapeutics, and molecular sensing. In parallel, the dynamic landscape of epitranscriptomic modifications, such as N⁶-methyladenosine (m⁶A), pseudouridine (Ψ), and 5-methylcytosine (m⁵C), has been recognized as a critical regulator of RNA structure, stability, and function. In this perspective article, we chart unexplored territories at the interface of these two mechanisms, focusing on how RNA modifications may influence aptamer folding or binding, and how aptamers could, in turn, be harnessed to detect or modulate the epitranscriptomic state. We also highlight opportunities for cross-disciplinary integration in synthetic biology, post-transcriptional regulation, and RNA-based therapeutics. While the direct regulatory connections between these domains remain to be fully elucidated, we propose their potential convergence as a fertile ground for innovation. The primary aim of this article is to stimulate discussion within and between these research communities and to attract attention toward a promising frontier for future investigations.