April 5, 2024 | Elsa Zacco, Laura Broglia, Misuzu Kurihara, Michele Monti, Stefano Gustincich, Annalisa Pastore, Kathrin Plath, Shinichi Nagakawa, Andrea Cerase, Natalia Sanchez de Groot, and Gian Gaetano Tartaglia
This comprehensive review explores the chemical principles governing RNA-mediated crowding events, commonly referred to as granules or biological condensates. It delves into the pivotal role of RNA sequence, structure, and chemical modifications in these processes, uncovering their correlation with crowding phenomena under physiological conditions. The review also investigates instances where crowding deviates from its intended function, leading to pathological consequences. By deepening our understanding of the delicate balance that governs molecular crowding driven by RNA and its implications for cellular homeostasis, the authors aim to shed light on this intriguing area of research. The review extends to methodologies used to decipher the composition and structural intricacies of RNA granules, offering a comprehensive overview of the techniques employed, including relevant computational approaches. Two detailed examples, *NEAT1* and *XIST*, highlight the significance of noncoding RNAs in the formation of phase-separated assemblies and their influence on cellular organization and function. The review elucidates the chemical underpinnings of RNA-mediated molecular crowding, investigates the role of modifications, structures, and composition of RNA granules, and explores both physiological and aberrant phase separation phenomena, providing a multifaceted understanding of the intriguing world of RNA-mediated biological condensates.This comprehensive review explores the chemical principles governing RNA-mediated crowding events, commonly referred to as granules or biological condensates. It delves into the pivotal role of RNA sequence, structure, and chemical modifications in these processes, uncovering their correlation with crowding phenomena under physiological conditions. The review also investigates instances where crowding deviates from its intended function, leading to pathological consequences. By deepening our understanding of the delicate balance that governs molecular crowding driven by RNA and its implications for cellular homeostasis, the authors aim to shed light on this intriguing area of research. The review extends to methodologies used to decipher the composition and structural intricacies of RNA granules, offering a comprehensive overview of the techniques employed, including relevant computational approaches. Two detailed examples, *NEAT1* and *XIST*, highlight the significance of noncoding RNAs in the formation of phase-separated assemblies and their influence on cellular organization and function. The review elucidates the chemical underpinnings of RNA-mediated molecular crowding, investigates the role of modifications, structures, and composition of RNA granules, and explores both physiological and aberrant phase separation phenomena, providing a multifaceted understanding of the intriguing world of RNA-mediated biological condensates.