Systematic Characterization of Stress-Induced RNA Granulation

Upon stress, cytoplasmic mRNA is sequestered to insoluble ribonucleoprotein (RNP) granules, such as the stress granule (SG). Partially due to the belief that translationally suppressed mRNAs are recruited to SGs in bulk, stress-induced dynamic redistribution of mRNA has not been thoroughly characterized. Here, we report that endoplasmic reticulum (ER) stress targets only a small subset of translationally suppressed mRNAs into the insoluble RNP granule fraction (RG). This subset, characterized by extended length and adenylate-uridylate (AU)-rich motifs, is highly enriched with genes critical for cell survival and proliferation. This pattern of RG targeting was conserved for two other stress types, heat shock and arsenite toxicity, which induce distinct responses in the total cytoplasmic transcriptome. Nevertheless, stress-specific RG-targeting motifs, such as guanylate-cytidylate (GC)-rich motifs in heat shock, were also identified. Previously underappreciated, transcriptome profiling in the RG may contribute to understanding human diseases associated with RNP dysfunction, such as cancer and neurodegeneration. [Display omitted] •Stresses target specific transcripts into the insoluble RNP granule fraction (RG)•Translational suppression is not the sole determinant for stress-induced RG targeting•AU-rich elements (AREs) promote RG targeting of transcripts during ER stress•Distinct stresses target similar but unique subsets of transcripts into the RG Namkoong et al. provide transcriptome-level snapshots of how different stresses regulate individual mRNA species between the soluble cytoplasm and insoluble RNA protein granule (RG). Several mRNA features, including transcript length and enrichment of ARE motifs, determine the specificity of RG targeting.