Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes

Summary: Stress granules are a conserved response of eukaryotic cells to environmental insults. These cytoplasmic ribonucleoprotein condensates have hitherto been primarily studied by microscopy, which showed previously that they comprise dense ∼200 nm cores embedded in a diffuse shell. We have deve...

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Main Authors: Natalia A. Demeshkina, Adrian R. Ferré-D’Amaré
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725005091
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author Natalia A. Demeshkina
Adrian R. Ferré-D’Amaré
author_facet Natalia A. Demeshkina
Adrian R. Ferré-D’Amaré
author_sort Natalia A. Demeshkina
collection DOAJ
description Summary: Stress granules are a conserved response of eukaryotic cells to environmental insults. These cytoplasmic ribonucleoprotein condensates have hitherto been primarily studied by microscopy, which showed previously that they comprise dense ∼200 nm cores embedded in a diffuse shell. We have developed large-scale purifications of budding yeast and mammalian (HEK293T cell) stress granule cores that do not rely on immunoprecipitation of candidate protein constituents. These unbiased preparations reveal that stress granule cores are discrete particles with variable size (average, 135 and 225 nm for yeast and human, respectively) and shape. Proteomics and transcriptomics demonstrate complex composition. The results of hybridization chain reaction fluorescence in situ hybridization (FISH) analyses in HEK293T cells are consistent with stress granule cores having heterogeneous composition, i.e., each stress granule core particle contains only a limited number of mRNA species. Biochemical purification now opens the way to mechanistic analysis of the heterogeneity and complexity of stress granules.
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spelling doaj-art-8edcae96a7a54cd58012d3947efb2ebb2025-08-20T03:48:18ZengElsevierCell Reports2211-12472025-06-0144611573810.1016/j.celrep.2025.115738Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomesNatalia A. Demeshkina0Adrian R. Ferré-D’Amaré1Laboratory of Nucleic Acids, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Corresponding authorLaboratory of Nucleic Acids, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Corresponding authorSummary: Stress granules are a conserved response of eukaryotic cells to environmental insults. These cytoplasmic ribonucleoprotein condensates have hitherto been primarily studied by microscopy, which showed previously that they comprise dense ∼200 nm cores embedded in a diffuse shell. We have developed large-scale purifications of budding yeast and mammalian (HEK293T cell) stress granule cores that do not rely on immunoprecipitation of candidate protein constituents. These unbiased preparations reveal that stress granule cores are discrete particles with variable size (average, 135 and 225 nm for yeast and human, respectively) and shape. Proteomics and transcriptomics demonstrate complex composition. The results of hybridization chain reaction fluorescence in situ hybridization (FISH) analyses in HEK293T cells are consistent with stress granule cores having heterogeneous composition, i.e., each stress granule core particle contains only a limited number of mRNA species. Biochemical purification now opens the way to mechanistic analysis of the heterogeneity and complexity of stress granules.http://www.sciencedirect.com/science/article/pii/S2211124725005091CP: Molecular biology
spellingShingle Natalia A. Demeshkina
Adrian R. Ferré-D’Amaré
Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
Cell Reports
CP: Molecular biology
title Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
title_full Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
title_fullStr Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
title_full_unstemmed Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
title_short Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
title_sort large scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes
topic CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124725005091
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AT adrianrferredamare largescalepurificationsrevealyeastandhumanstressgranulecoresareheterogeneousparticleswithcomplextranscriptomesandproteomes