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High-throughput Screening for Protein-based Inheritance in S. cerevisiae

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

A Non-amyloid Prion Particle that Activates a Heritable Gene Expression Program.

Anupam K Chakravarty¹, Tina Smejkal¹, Alan K Itakura²

¹Department of Chemical and Systems Biology, Stanford University, 269 Campus Drive, Stanford, CA 94305, USA.

|November 24, 2019

Summary

The disordered region of the Vts1 protein self-assembles into infectious, non-amyloid condensates called [SMAUG+]. This protein-based epigenetic element enhances gene regulation and confers adaptive traits in yeast.

Keywords:

IDPs RNA-binding proteins epigenetics non-amyloid prions phase separation post-transcriptional gene regulation

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Area of Science:

Molecular Biology
Epigenetics
Protein Self-Assembly

Background:

Spatiotemporal gene regulation relies on RNA-binding proteins with intrinsically disordered regions.
The ancient developmental regulator Vts1/Smaug possesses such a disordered region.

Purpose of the Study:

To investigate the self-assembly properties of the Vts1 disordered region.
To determine if these self-assemblies function as epigenetic elements.
To explore the functional consequences of Vts1 self-assembly.

Main Methods:

Analysis of Vts1 protein self-assembly into gel-like condensates.
Characterization of these condensates as non-amyloid prions ([SMAUG+]).
Assessing the impact of [SMAUG+] on mRNA decay and gene expression networks in yeast.

Main Results:

The disordered region of Vts1 drives self-assembly into infectious, non-amyloid condensates ([SMAUG+]).
Vts1 condensation enhances its mRNA decay function and is evolutionarily conserved.
Yeast cells with [SMAUG+] exhibit altered mRNA profiles and improved growth under nutrient limitation.
Purified Vts1 condensates can induce [SMAUG+] in naive cells.

Conclusions:

Non-amyloid self-assembly of RNA-binding proteins can mediate a novel form of epigenetics.
This protein-based epigenetics enables heritable, adaptive gene expression programs.
Vts1 condensates represent a functional prion that influences cellular traits.