Function and Dysfunction of Phase Separations and Transitions Driven by Intrinsically Disordered Protein Regions

Dear Colleagues,

In the last decade, it has become increasingly evident that intrinsically disordered protein regions (IDPRs), either alone or in the presence of nucleic acids, have the ability to undergo liquid–liquid phase separation (LLPS), a process also known as de-mixing and leading to the formation of a condensed phase surrounded by, and dynamically interchanging with, a dispersed phase. LLPS, which has been found to occur in the cell cytoplasm, in the nucleoplasm, as well as in vitro for many purified proteins, has attracted much interest, as it drives the formation of membrane-less organelles (MLOs) (e.g., Cajal bodies, processing bodies, nucleolus, stress granules, centrosomes and aggresomes), whose function is essential for the cell and whose dysfunction is associated with various pathologies, including age-related disorders. Indeed, these biological condensates play a critical role in the spatiotemporal organization of the cell, where they exert a multitude of key biological functions, ranging from transcriptional regulation and silencing to the control of signal transduction networks. Compelling experimental evidence gathered in the last decade has converged to show that phase separation is a ubiquitous principle in cellular organization, underlying many biological processes, the list of which is growing rapidly. These liquid condensates can undergo “maturation” towards a gel or solid state, the phenomenon being referred to as phase transition. This transition is often associated with a pathological condition. IDPRs are indeed known to form amyloid-like structures via the formation of hydrogels. Beyond the formation of MLOs, LLPS also underlies the formation of viral factories, i.e., liquid-like inclusions in which viral transcription and replication, as well as assembly, take place.

The growing number of research articles focused on LLPS (now approaching 3000) has contributed, in the last decade, to highlighting the physiological and pathological relevance of LLPS. The aim of this Special Issue is to contribute to the development of the field and fuel additional studies aimed at gathering information on proteins undergoing LLPS in a structured and knowledgeable manner, while providing a wide range of information on the biophysical driving forces, the biological function and the regulation of these systems.

Dr. Sonia Longhi
Prof. Dr. Stefano Gianni
Guest Editors

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• intrinsically disordered proteins and protein regions
• liquid–liquid phase separation
• phase transition and fibrillation
• membrane-less organelles
• liquid-like viral factories.