A tale of (disordered) tail

Abstract

Although liquid-liquid phase separation (LLPS) has been extensively studied in various cellular and organismal contexts, the link between functional influence of a genetic mutation and LLPS with respect to human diseases is poorly understood. A recent article by Mensah et al. looks at a rare genetic disease to identify a frameshift mutation, which triggered aberrant phase separation and nucleolar dysregulation, linking genetic variants to a dysregulation of biomolecular condensates.

Fig. 1. Schematic representation of HMGB1 phase separation and its link with BPTAS.

a Cartoon representation of wt-HMGB1 with ~60 amino acids long acidic disordered tail. b Cartoon representation of fs-HMGB1 in which acidic tail is converted into an arginine-rich basic tail. c wt-HMGB1 phase separates into dynamic, spherical liquid droplets. d Aberrant phase separation of fs-HMGB1 produces dynamically arrested droplets both in vitro & in vivo. Credit: Sumangal Roychowdhury.