mRNAs sequestered in stress granules recover nearly completely for translation

Stress granules (SGs) are membrane-less condensates composed of RNA and protein that assemble in response to stress stimuli and disassemble when stress is lifted. Both assembly and disassembly are tightly controlled processes, yet, it remains elusive whether mRNAs in SGs completely recover for translation following stress relief. Using RNA-seq of translating fractions in human cell line, we found that higher fraction of the m⁶A-modified mRNAs recovered for translation compared to unmodified mRNAs, i.e. 95% vs 84%, respectively. Considering structural mRNA analysis, we found that the m⁶A modification enhances structuring at nucleotides in its close vicinity. Our results suggest that SG-sequestered mRNAs disassemble nearly completely from SGs and the m⁶A modification may display some advantage to the mRNAs in their recovery for translation likely by m⁶A-driven structural stabilization.