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The stress granule transcriptome reveals principles of mRNA accumulation in stress granules.

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Stress granules are mRNA-protein assemblies formed on nontranslating mRNAs. Stress granules are important in the stress response, related to neuronal mRNP granules, and aberrant stress granules contribute to some degenerative diseases. By RNA-Seq and single molecule FISH, we describe the stress granule transcriptome in both yeast and mammalian cells. This reveals that while essentially every mRNA, and some ncRNAs, can be targeted to stress granules, the efficiency of targeting can vary from <1% to 73%. mRNA accumulation in stress granules is increased by longer coding regions, poor translatability, and correlates with some RNA binding proteins. Standardizing the RNA-Seq analysis by single molecule FISH allows a quantitative description of the general and stress gra­nule transcriptome. Approximately 15% of the bulk mRNA molecules accumulate in stress granules suggesting their effect will be limited primarily to subsets of mRNAs highly accumulating in stress granules

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