Liquid liquid phase separation

In this Mini Review, the authors discuss the relationship between condensate formation, genome organization, and transcriptional activity, focusing on the experimental evidence behind the role of transcriptional condensates in gene regulation.

This Perspective discusses how biomolecular condensates are co-evolving as complex microcompartments alongside membrane-bound organelles in cells.

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.

An investigation of tau’s phase separation propensity and interactions with DNA, nucleosome arrays, and heterochromatin proteins shows that these properties are dependent on tau’s phosphorylation state.

This article presents a hitherto unknown role of a-Synuclein protein to function as a Pickering agent for TDP-43-RNA biomolecular condensates to emulsify them towards heterotypic amyloid fibrils.

Theoretical modeling and experimental tests shed light on the roles of nascent prerRNA, produced by Pol I transcription, in the assembly of the sea-island multi-phase structure in the nucleolus.

Atomistic modeling of dense solutions of γ-crystallins links liquid-liquid phase equilibrium to amino-acid sequence and predicts mutations for altering the critical temperature.

The long non-classical cadherin-23 forms cis-clusters on a membrane via transient, weak, but multivalent and spatially distributed hydrophobic interactions.

In a breast cancer cell line migrating through microchannels, stress-responsive paraspeckle numbers increase under confinement and polarize towards the leading edge.

Stable hetero-complexes exist in the dilute phase of phase-separating algal pyrenoid proteins in vitro.

Raman spectroscopy is employed to show simultaneous, label-free imaging of RNA, DNA, and proteins, revealing secondary structural features of intracellular LLPS organelles, and condensed chromosome.

Probing ssDNA binding to TAR-DNA-binding protein-43 (TDP-43) prion-like domain (PLD) through NMR shows key interactions for nucleic acid to drive liquid-liquid phase separation (LLPS) of intrinsically-disordered proteins.

The phase separation behaviour of non-structure protein nsp8 of SARS CoV2 in the primer synthesis mechanism is presented, underpinning the replication of coronavirus.

Generative autoencoders create full conformational ensembles of intrinsically disordered proteins from short molecular dynamics simulations.