Deciphering the RNA Landscape of RNA Granules

Abstract

RNA granules, including stress granules (SGs) and processing bodies (PBs), are membraneless organelles that orchestrate RNA localization, metabolism, and translational control in response to cellular stress. This Perspective examines the RNA landscape within SGs and PBs, highlighting recent insights into how these compartments shape RNA fate. We review current methodologies for probing granule-associated RNAs, including high-resolution imaging, transcriptomics, and sequencing-based approaches. In particular, we spotlight emerging photoactivated proximity labeling techniques that offer unprecedented spatiotemporal resolution for mapping RNA interactions in living cells. Looking ahead, we propose combining multiomic approaches to better define the roles of RNAs within granules. Finally, we emphasize the importance of investigating RNA granules in neuronal contexts, where dysregulated RNA condensation is intimately linked to neurodegenerative diseases. Together, these approaches promise to elucidate the molecular logic by which RNA granules govern post-transcriptional gene regulation and cellular adaptation to stress.