Molecular Cell
Volume 68, Issue 4, 16 November 2017, Pages 808-820.e5
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The Stress Granule Transcriptome Reveals Principles of mRNA Accumulation in Stress Granules

https://doi.org/10.1016/j.molcel.2017.10.015Get rights and content
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Highlights

  • Purification of stress granule cores identifies RNAs in stress granules

  • Only ∼10% of bulk mRNA molecules are present in stress granules

  • Most mRNAs go to stress granules, but the efficiency varies from <1% to >95%

  • Poor translation efficiency and longer length correlate with targeting to granules

Summary

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

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

Cited by (0)

3

Present address: Department of Biological Chemistry, University of California, Los Angeles, CA 90024, USA

4

Present address: Department of Chemistry and Biochemistry, Loyola Marymount University, Los Angeles, CA 90045, USA

5

These authors contributed equally

6

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