Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3T 1J4, Canada.
The Department of Biophysics and Biophysical Chemistry, the Solomon Snyder Department of Neuroscience, Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA.
Mol Cell. 2018 Nov 15;72(4):727-738.e5. doi: 10.1016/j.molcel.2018.10.010. Epub 2018 Nov 8.
mRNAs form ribonucleoprotein complexes (mRNPs) by association with proteins that are crucial for mRNA metabolism. While the mRNP proteome has been well characterized, little is known about mRNP organization. Using a single-molecule approach, we show that mRNA conformation changes depending on its cellular localization and translational state. Compared to nuclear mRNPs and lncRNPs, association with ribosomes decompacts individual mRNAs, while pharmacologically dissociating ribosomes or sequestering them into stress granules leads to increased compaction. Moreover, translating mRNAs rarely show co-localized 5' and 3' ends, indicating either that mRNAs are not translated in a closed-loop configuration, or that mRNA circularization is transient, suggesting that a stable closed-loop conformation is not a universal state for all translating mRNAs.
mRNA 通过与对 mRNA 代谢至关重要的蛋白质结合形成核糖核蛋白复合物 (mRNP)。虽然 mRNP 蛋白质组已经得到很好的描述，但对于 mRNP 的组织知之甚少。我们使用单分子方法表明，mRNA 的构象取决于其细胞定位和翻译状态。与核 mRNP 和 lncRNP 相比，与核糖体的结合会使单个 mRNA 解压缩，而药理学上分离核糖体或将其隔离到应激颗粒中会导致 mRNA 进一步压缩。此外，翻译的 mRNA 很少显示共定位的 5' 和 3' 端，这表明 mRNA 不是以闭环构型进行翻译，或者 mRNA 环化是短暂的，这表明稳定的闭环构象不是所有翻译的 mRNA 的普遍状态。
