On the role of phase separation in the biogenesis of membraneless compartments. (2nd February 2022)

• Record Type: Journal Article
• Authors: Musacchio, Andrea
• Is Part Of: EMBO journal. Volume 41:Number 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-02
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2021109952
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract : Molecular mechanistic biology has ushered us into the world of life's building blocks, revealing their interactions in macromolecular complexes and inspiring strategies for detailed functional interrogations. The biogenesis of membraneless cellular compartments, functional mesoscale subcellular locales devoid of strong internal order and delimiting membranes, is among mechanistic biology's most demanding current challenges. A developing paradigm, biomolecular phase separation, emphasizes solvation of the building blocks through low‐affinity, weakly adhesive unspecific interactions as the driver of biogenesis of membraneless compartments. Here, I discuss the molecular underpinnings of the phase separation paradigm and demonstrate that validating its assumptions is much more challenging than hitherto appreciated. I also discuss that highly specific interactions, rather than unspecific ones, appear to be the main driver of biogenesis of subcellular compartments, while phase separation may be harnessed locally in selected instances to generate material properties tailored for specific functions, as exemplified by nucleocytoplasmic transport. Abstract : This commentary contrasts the contributions of site‐specific versus unspecific biomolecular interactions to the molecular mechanisms of subcellular compartment assembly and function.