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Tau Condensates.

Kenneth S Kosik1,2,3, Songi Han4,5,6

  • 1Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA. kosik@lifesci.ucsb.edu.

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|February 26, 2020
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Summary
This summary is machine-generated.

Intrinsically disordered proteins like tau can undergo liquid-liquid phase separation (LLPS) with RNA. This tau-RNA complex coacervation is reversible and may play a physiological role in neurodegenerative diseases.

Keywords:
CoacervationElectron paramagnetic resonanceFrontotemporal dementiaLiquid-liquid phase separationMembraneless organellesRNATau droplets

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Proteins, especially intrinsically disordered ones, often undergo liquid-liquid phase separation (LLPS).
  • LLPS is crucial for cellular compartmentalization and molecular reactions.
  • Certain intrinsically disordered proteins form pathological inclusions in neurodegenerative diseases, such as tau in tauopathies.

Purpose of the Study:

  • To investigate the interaction between tau protein and RNA species.
  • To explore the role of tau-RNA liquid-liquid phase separation (LLPS) in cellular function and disease.

Main Methods:

  • Studied the association of tau protein with RNA, specifically tRNA.
  • Investigated tau-RNA complex coacervation under charge-matching conditions.
  • Monitored the reversibility and fibrillization potential of tau-RNA LLPS droplets over time using thioflavin T.

Main Results:

  • Tau protein selectively binds to RNA, including tRNA, with high affinity (nanomolar dissociation constant).
  • Tau and RNA undergo reversible LLPS via complex coacervation under specific conditions.
  • Tau-RNA LLPS condensates can either dissolve or transition to a fibrillar state, indicated by β-sheet content, over extended periods.

Conclusions:

  • Tau-RNA LLPS is a dynamic process that can be regulated.
  • Phase-separated tau-RNA condensates may represent an intermediate state on the pathway to tau fibrillization.
  • The physiological and pathological relevance of tau-RNA phase separation warrants further investigation in neurodegenerative conditions like Alzheimer's disease.