mRNP architecture in translating and stress conditions reveals an ordered pathway of mRNP compaction.
mRNP architecture in translating and stress conditions reveals an ordered pathway of mRNP compaction.
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DOI：
10.1083/jcb.201806183
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发表时间：
2018-12-03
期刊：
影响因子：
--
通讯作者：
Parker R
中科院分区：
文献类型：
--
作者：
Khong A;Parker R
Khong和帕克使用单分子FISH来检查mRNA进入应激颗粒的时间以及mRNA蛋白复合物（mRNP）结构。核糖体径流后mRNA压缩增加，这表明mRNP在非翻译条件下优先采用闭环结构。应激颗粒（Stress granules，SGs）是应激过程中形成的非翻译mRNA-蛋白复合物（nontranslating mRNA-protein complex，mRNP）的瞬时无膜细胞器。在这项研究中，我们使用了多个单分子FISH探针的特定mRNA，以检查他们的SG招聘和空间组织。SG进入需要核糖体流出，因为长开放阅读框（ORF）mRNA在SG积累中延迟，表明SG转录组随时间变化。此外，mRNA在翻译时从预期的线性长度压缩20倍，并在核糖体流出期间从5′端开始以逐步方式进一步压缩20倍。令人惊讶的是，检测的mRNA的5′和3′末端在翻译时分离，但在非翻译条件下，长ORF mRNA的末端变得接近，这表明mRNP的闭环模型优先在非翻译mRNA上形成。无核糖体mRNA的压缩是ATP独立的，与通过RNA结构形成发生的压缩一致。这些结果表明，翻译抑制触发了mRNP重组，使末端更接近，这与3′ UTR元件和poly（A）尾对mRNA稳定性和翻译的调节有关。
Khong and Parker use single-molecule FISH to examine the timing of mRNA entry to stress granule as well as mRNA protein complex (mRNP) architecture. mRNA compaction increases after ribosome runoff, suggesting that mRNPs preferentially adopt a closed-loop structure in nontranslating conditions. Stress granules (SGs) are transient membraneless organelles of nontranslating mRNA–protein complexes (mRNPs) that form during stress. In this study, we used multiple single-molecule FISH probes for particular mRNAs to examine their SG recruitment and spatial organization. Ribosome runoff is required for SG entry, as long open reading frame (ORF) mRNAs are delayed in SG accumulation, indicating that the SG transcriptome changes over time. Moreover, mRNAs are ∼20× compacted from an expected linear length when translating and compact ∼2-fold further in a stepwise manner beginning at the 5′ end during ribosome runoff. Surprisingly, the 5′ and 3′ ends of the examined mRNAs were separated when translating, but in nontranslating conditions the ends of long ORF mRNAs become close, suggesting that the closed-loop model of mRNPs preferentially forms on nontranslating mRNAs. Compaction of ribosome-free mRNAs is ATP independent, consistent with compaction occurring through RNA structure formation. These results suggest that translation inhibition triggers an mRNP reorganization that brings ends closer, which has implications for the regulation of mRNA stability and translation by 3′ UTR elements and the poly(A) tail.
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