Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
Cell. 2020 Dec 23;183(7):1801-1812.e13. doi: 10.1016/j.cell.2020.11.010. Epub 2020 Dec 11.
Cellular stress leads to reprogramming of mRNA translation and formation of stress granules (SGs), membraneless organelles consisting of mRNA and RNA-binding proteins. Although the function of SGs remains largely unknown, it is widely assumed they contain exclusively non-translating mRNA. Here, we re-examine this hypothesis using single-molecule imaging of mRNA translation in living cells. Although we observe non-translating mRNAs are preferentially recruited to SGs, we find unequivocal evidence that mRNAs localized to SGs can undergo translation. Our data indicate that SG-associated translation is not rare, and the entire translation cycle (initiation, elongation, and termination) can occur on SG-localized transcripts. Furthermore, translating mRNAs can be observed transitioning between the cytosol and SGs without changing their translational status. Together, these results demonstrate that mRNA localization to SGs is compatible with translation and argue against a direct role for SGs in inhibition of protein synthesis.
细胞应激会导致 mRNA 翻译的重新编程,并形成应激颗粒(SGs),这是一种由 mRNA 和 RNA 结合蛋白组成的无膜细胞器。尽管 SGs 的功能在很大程度上仍不清楚,但人们普遍认为它们只包含非翻译的 mRNA。在这里,我们使用活细胞中单分子 mRNA 翻译成像技术重新检验了这一假设。尽管我们观察到非翻译的 mRNAs 优先被招募到 SGs 中,但我们发现确凿的证据表明定位到 SGs 的 mRNAs 可以进行翻译。我们的数据表明,SG 相关的翻译并不罕见,整个翻译周期(起始、延伸和终止)都可以在 SG 定位的转录本上进行。此外,我们可以观察到翻译中的 mRNAs 在不改变其翻译状态的情况下在细胞质和 SGs 之间转换。总之,这些结果表明,mRNA 定位到 SGs 与翻译是兼容的,并反对 SGs 在抑制蛋白质合成中的直接作用。