Unravelling the Interplay between Biomolecular Condensates and RNA in Cancer and Diseases

Abstract

Biomolecular condensates (BCs), including membraneless organelles, are basically Ribonucleic acid (RNA)-protein complexes that are emerging as a potential candidate because of its paramount significance in revealing fundamentals of cell biology and pathology including cancer. Aiming to understand its importance, scientists are dealing with it in an interdisciplinary manner—from polymer chemistry to genetics. Over time the mechanism of liquid-liquid phase separation (LLPS) and the model of ‘Stickers and Spacers’ have widened our understanding and broadened our scope of approaches to get insights into these molecular entities. RNA molecules and its specific partner proteins, certain ribonucleoproteins (RNPs), play pivotal roles in different trajectories of BCs, i.e., in localization, compartmentalization, epigenetic regulation, and dynamics. However, several aspects need to be made clearer to tackle human diseases including cancer. In addition to the RNAs, in this review specific aspects of the BCs are presented in the context of neurodegenerative diseases, viral infections and cancer, and their link with stress granules (SG), P bodies, paraspeckles, and host encoded and viral encoded non-coding RNAs, discussing cancer associated proteins, tumour suppressors and repressors, dysregulation of cancer signals, and role of super enhancers. A special focus is reserved to oncolytic viruses and epidemic viruses, through the intervention on stress granule protein partners, virus-formed intracellular condensates, and viral RNAs. The review covers not only the basics of BCs but also encompasses the emerging context of condensate-targeted drug discovery and cancer therapeutics by means of Proteolysis-targeting chimera (PROTAC), Ribonuclease-targeting chimera (RIBOTAC), small molecule inhibitors of protein-RNA interactions, Antisense oligonucleotides (ASO) and compounds targeting non-coding RNA (ncRNA) triple helix, determining RNA degradation.