Lighting Up Endogenous RNA: Fluorescent Aptamer Sensors for Live-Cell Imaging

Endogenous RNAs orchestrate cellular processes through precise spatiotemporal regulation, and live-cell imaging of these molecules is essential for dissecting their roles in gene expression, disease progression, and cellular homeostasis. While traditional methods rely on exogenous labeling or fixation, fluorescent RNA aptamer-based sensors have emerged as transformative tools for visualizing endogenous RNAs in their native context. These sensors allow real-time tracking of mRNA localization, miRNA activity, and RNA–protein interactions with minimal disturbance. However, challenges such as the requirement for exogenous fluorogenic dyes, limited brightness, photostability, and target specificity in complex cellular environments hinder their wider application. This review provides a comprehensive overview of recent advances in fluorescent RNA aptamer-based sensors, discussing the design principles, mechanisms of fluorescence activation, and their application in live-cell RNA imaging. We also address the current limitations and future directions for improving these sensors, highlighting their transformative potential in RNA biology and their implications for diagnostic and therapeutic strategies.