RNA Controls PolyQ Protein Phase Transitions

Mol Cell. 2015 Oct 15;60(2):220-30. doi: 10.1016/j.molcel.2015.09.017.

Abstract

Compartmentalization in cells is central to the spatial and temporal control of biochemistry. In addition to membrane-bound organelles, membrane-less compartments form partitions in cells. Increasing evidence suggests that these compartments assemble through liquid-liquid phase separation. However, the spatiotemporal control of their assembly, and how they maintain distinct functional and physical identities, is poorly understood. We have previously shown an RNA-binding protein with a polyQ-expansion called Whi3 is essential for the spatial patterning of cyclin and formin transcripts in cytosol. Here, we show that specific mRNAs that are known physiological targets of Whi3 drive phase separation. mRNA can alter the viscosity of droplets, their propensity to fuse, and the exchange rates of components with bulk solution. Different mRNAs impart distinct biophysical properties of droplets, indicating mRNA can bring individuality to assemblies. Our findings suggest that mRNAs can encode not only genetic information but also the biophysical properties of phase-separated compartments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Compartmentation
  • Cyclins / chemistry
  • Cyclins / genetics
  • Cyclins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression
  • Gene Expression Regulation, Fungal*
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Organelles / chemistry
  • Organelles / metabolism
  • Peptides / chemistry*
  • Peptides / metabolism
  • Phase Transition
  • RNA, Fungal / metabolism*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Rheology
  • Saccharomycetales / chemistry
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism*

Substances

  • Cyclins
  • Fungal Proteins
  • Microfilament Proteins
  • Peptides
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • polyglutamine