Molecular Cell
Volume 57, Issue 5, 5 March 2015, Pages 936-947
Journal home page for Molecular Cell

Article
Phase Transition of a Disordered Nuage Protein Generates Environmentally Responsive Membraneless Organelles

https://doi.org/10.1016/j.molcel.2015.01.013Get rights and content
Under a Creative Commons license
open access

Highlights

  • Intrinsically disordered N terminus of Ddx4 forms organelles in cells and in vitro

  • Phase transition to form organelles is driven by electrostatic interactions

  • Methylation, ionic strength, and temperature changes can dissolve the organelles

  • Sequence determinants of formation are common in membraneless organelle proteins

Summary

Cells chemically isolate molecules in compartments to both facilitate and regulate their interactions. In addition to membrane-encapsulated compartments, cells can form proteinaceous and membraneless organelles, including nucleoli, Cajal and PML bodies, and stress granules. The principles that determine when and why these structures form have remained elusive. Here, we demonstrate that the disordered tails of Ddx4, a primary constituent of nuage or germ granules, form phase-separated organelles both in live cells and in vitro. These bodies are stabilized by patterned electrostatic interactions that are highly sensitive to temperature, ionic strength, arginine methylation, and splicing. Sequence determinants are used to identify proteins found in both membraneless organelles and cell adhesion. Moreover, the bodies provide an alternative solvent environment that can concentrate single-stranded DNA but largely exclude double-stranded DNA. We propose that phase separation of disordered proteins containing weakly interacting blocks is a general mechanism for forming regulated, membraneless organelles.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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