Fig. 2

Molecular basis for membrane-less organelles assembly. The proteins enriched within the matrices of membrane-less organelles commonly exhibit multiple modules that create multivalency, including folded binding domains (red) and low complexity regions (purple). Valency is often amplified by domains that enable homo-, or hetero-oligomerization (orange). Interactions between proteins containing different combinations of these interaction modules provide a framework for building a heterogeneous, infinitely expandable network within membrane-less organelles. Formation of this type of network drives phase separation when the critical concentration threshold is reached. For many of the examples discussed herein, active RNA transcription is needed for membrane-less organelle assembly. We hypothesize that expression of RNA in excess of a critical concentration threshold is needed to nucleate interactions with specific, multi-modular proteins, and for nucleating formation of membrane-less organelles. Stress signals can alter the multivalent interactions that drive phase separation and lead to partial or complete disassembly of the organelle