Interplay Between Protein-RNA Binding and Phase Separation Drives Emergent Behavior in RNP Condensates

Protein-RNA binding and biomolecular condensation are two key processes underlying the assembly and function of ribonucleoprotein (RNP) condensates. However, the understanding of the physical consequences of their interplay is still incomplete. To investigate this coupling, here we develop a minimal coarse-grained molecular model that combines specific, saturable protein-RNA binding with multivalent protein-protein interactions. Our results show that RNA acts as a molecular scaffold whose ability to promote condensation depends on the distribution of bound proteins across RNA molecules. This provides a simple microscopic explanation for both RNA-length-dependent condensation and re-entrant phase behavior, showing that condensate dissolution at high RNA concentration can emerge from entropic effects without requiring explicit electrostatic interactions. Conversely, condensate assembly markedly enhances effective protein-RNA binding, demonstrating that substantial changes in binding behavior can emerge without changes in intrinsic affinity. This provides a general physical mechanism through which condensates can reshape molecular competition between RNA-binding proteins. Together, these findings establish a framework linking RNA binding and biomolecular condensation, illustrating how their interplay governs condensate assembly.