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Mol Cell. 2017 Nov 16;68(4):808-820.e5. doi: 10.1016/j.molcel.2017.10.015. Epub 2017 Nov 9.

The Stress Granule Transcriptome Reveals Principles of mRNA Accumulation in Stress Granules.

Author information

1
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
2
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
3
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA. Electronic address: roy.parker@colorado.edu.

Abstract

Stress granules are mRNA-protein assemblies formed from nontranslating mRNAs. Stress granules are important in the stress response and may contribute to some degenerative diseases. Here, we describe the stress granule transcriptome of yeast and mammalian cells through RNA-sequencing (RNA-seq) analysis of purified stress granule cores and single-molecule fluorescence in situ hybridization (smFISH) validation. While essentially every mRNA, and some noncoding RNAs (ncRNAs), can be targeted to stress granules, the targeting efficiency varies from <1% to >95%. mRNA accumulation in stress granules correlates with longer coding and UTR regions and poor translatability. Quantifying the RNA-seq analysis by smFISH reveals that only 10% of bulk mRNA molecules accumulate in mammalian stress granules and that only 185 genes have more than 50% of their mRNA molecules in stress granules. These results suggest that stress granules may not represent a specific biological program of messenger ribonucleoprotein (mRNP) assembly, but instead form by condensation of nontranslating mRNPs in proportion to their length and lack of association with ribosomes.

KEYWORDS:

RNA localization; RNA-seq; RNP granules; amyotrophic lateral sclerosis; eCLIP; mRNP assemblies; neurodegenerative diseases; single molecule FISH; stress granules

PMID:
29129640
PMCID:
PMC5728175
DOI:
10.1016/j.molcel.2017.10.015
[Indexed for MEDLINE]
Free PMC Article

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