A Non-Amyloid Prion Particle that Activates a Heritable Gene Expression Program.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA576380 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10244474.fastq.gz | Fastqsanger.gz | |||
| SRR10244475.fastq.gz | Fastqsanger.gz | |||
| SRR10244476.fastq.gz | Fastqsanger.gz | |||
| SRR10244477.fastq.gz | Fastqsanger.gz | |||
| SRR10244478.fastq.gz | Fastqsanger.gz |
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Project description:Spatiotemporal gene regulation is often driven by RNA-binding proteins that harbor long intrinsically disordered regions in addition to folded RNA-binding domains. We report that the disordered region of the evolutionarily ancient developmental regulator Smaug drives selfassembly into gel-like condensates. These proteinaceous particles are not composed ofamyloid. Yet they are infectious, allowing them to act as a protein-based epigenetic element: a prion. In contrast to many amyloid prions, condensation of Smaug enhances its function in mRNA decay, and its self-assembly properties are conserved over large evolutionary distances. Yeast cells harboring the [SMAUG+] prion downregulate a coherent network of mRNAs and exhibit improved growth under nutrient limitation. Smaug condensates formed from purified protein can transform naïve cells to acquire the prion. Our data establish that non-amyloid selfassembly of RNA-binding proteins can drive a form of epigenetics beyond the chromosome, instilling adaptive gene expression programs that are heritable over long biological timescales.
2020-02-05 | GSE138557 | GEO
Project description:Spatiotemporal gene regulation is often driven by RNA-binding proteins that harbor long intrinsically disordered regions in addition to folded RNA-binding domains. We report that the disordered region of the evolutionarily ancient developmental regulator Vts1/Smaug drives self-assembly into gel-like condensates. These proteinaceous particles are not composed of amyloid, yet they are infectious, allowing them to act as a protein-based epigenetic element: a prion [SMAUG+]. In contrast to many amyloid prions, condensation of Vts1 enhances its function in mRNA decay, and its self-assembly properties are conserved over large evolutionary distances. Yeast cells harboring [SMAUG+] downregulate a coherent network of mRNAs and exhibit improved growth under nutrient limitation. Vts1 condensates formed from purified protein can transform naive cells to acquire [SMAUG+]. Our data establish that non-amyloid self-assembly of RNA-binding proteins can drive a form of epigenetics beyond the chromosome, instilling adaptive gene expression programs that are heritable over long biological timescales.
| S-EPMC6980676 | biostudies-literature
Project description:Hingant2014 - Micellar On-Pathway
Intermediate in Prion Amyloid Formation
Hingant2014 - Micellar On-Pathway
Intermediate in Prion Amyloid Formation
Encoded
non-curated model. Issues:
-
Missing kinetic parameters
This model is described in the article:
A micellar on-pathway
intermediate step explains the kinetics of prion amyloid
formation.
Hingant E, Fontes P,
Alvarez-Martinez MT, Arnaud JD, Liautard JP, Pujo-Menjouet
L.
PLoS Comput. Biol. 2014 Aug; 10(8):
e1003735
Abstract:
In a previous work by Alvarez-Martinez et al. (2011), the
authors pointed out some fallacies in the mainstream
interpretation of the prion amyloid formation. It appeared
necessary to propose an original hypothesis able to reconcile
the in vitro data with the predictions of a mathematical model
describing the problem. Here, a model is developed accordingly
with the hypothesis that an intermediate on-pathway leads to
the conformation of the prion protein into an amyloid competent
isoform thanks to a structure, called micelles, formed from
hydrodynamic interaction. The authors also compare data to the
prediction of their model and propose a new hypothesis for the
formation of infectious prion amyloids.
This model is hosted on
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and identified by:
MODEL1409230001.
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To the extent possible under law, all copyright and related or
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Project description:Organisms often commit to one of two strategies: living fast and dying young or living slow and dying old. In fluctuating environments, however, switching between these two strategies could be advantageous. Lifespan is often inversely correlated with cell size and proliferation, which are both limited by protein synthesis. Here we report that a highly conserved RNA-modifying enzyme, the pseudouridine synthase Pus4/TruB, can act as a prion, endowing yeast with greater proliferation rates at the cost of a shortened lifespan. Cells harboring the prion can grow larger and exhibit altered protein synthesis. This epigenetic state, [BIG+] (better in growth), allows cells to heritably yet reversibly alter their translational program, leading to the differential expression of hundreds of proteins, including many that regulate proliferation and aging. Our data reveal a functional role for aggregation of RNA-modifying enzymes in driving heritable epigenetic states that transform cell growth and survival.
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