Mitochondrial RNA sequencing
RNA granules are liquid-liquid phase-separated condensates comprising RNA and proteins. Despite increasing elucidation of their biological functions, studies have predominantly relied on biological methodologies, lacking adequate chemical tools. Here, we propose a concept for identifying chemical probes to characterize RNA granules of interest among nucleic acid-targeting agents (ICP-CHARGINGS). Focusing on mitochondrial RNA granules (MRGs), whose functions remain elusive, we developed a methodology within this framework and identified NATA, a new fluorescent molecule that binds to the mitoribosome, enabling MRG labeling and recognition. Utilizing NATA as the probe, we demonstrated a close correlation between MRG maintenance and assembly with cellular survival and proliferation under cold shock and hypoxic stress. Overall, the introduction and implementation of the ICP-CHARGINGS strategy in this investigation not only yield a specialized chemical tool to advance our comprehension of MRG biology but also stimulate avenues for developing tailored chemical probes targeting diverse RNA granules in future investigations