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.

应激颗粒（Stress granules, SGs）是一类由RNA与蛋白质构成的无膜凝聚体，可响应应激刺激发生组装，并在应激解除后解离。尽管其组装与解离过程均受到严格调控，但目前仍不清楚，应激解除后滞留在SGs中的mRNA是否可完全恢复翻译活性。通过对人类细胞系中翻译组分进行RNA测序（RNA-seq）分析，我们发现经N⁶-甲基腺嘌呤（m⁶A）修饰的mRNA，其翻译恢复比例高于未修饰mRNA，二者分别为95%与84%。结合mRNA结构分析，我们发现m⁶A修饰可增强其邻近核苷酸区域的结构稳定性。本研究结果表明，被SGs捕获的mRNA几乎可完全从颗粒中解离；而m⁶A修饰或可通过其介导的结构稳定作用，赋予mRNA在翻译恢复进程中的优势。