Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Computer Science and Electrical Engineering Department, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Struct Mol Biol. 2018 Aug;25(8):677-686. doi: 10.1038/s41594-018-0091-z. Epub 2018 Jul 30.
RNA folding plays a crucial role in RNA function. However, knowledge of the global structure of the transcriptome is limited to cellular systems at steady state, thus hindering the understanding of RNA structure dynamics during biological transitions and how it influences gene function. Here, we characterized mRNA structure dynamics during zebrafish development. We observed that on a global level, translation guides structure rather than structure guiding translation. We detected a decrease in structure in translated regions and identified the ribosome as a major remodeler of RNA structure in vivo. In contrast, we found that 3' untranslated regions (UTRs) form highly folded structures in vivo, which can affect gene expression by modulating microRNA activity. Furthermore, dynamic 3'-UTR structures contain RNA-decay elements, such as the regulatory elements in nanog and ccna1, two genes encoding key maternal factors orchestrating the maternal-to-zygotic transition. These results reveal a central role of RNA structure dynamics in gene regulatory programs.
RNA 折叠在 RNA 功能中起着至关重要的作用。然而，对转录组的全局结构的了解仅限于稳态细胞系统，从而阻碍了对生物转变过程中 RNA 结构动力学及其如何影响基因功能的理解。在这里，我们描述了斑马鱼发育过程中 mRNA 结构动力学。我们观察到，在全局水平上，翻译指导结构而不是结构指导翻译。我们检测到翻译区域结构的减少，并确定核糖体是体内 RNA 结构的主要重塑剂。相比之下，我们发现 3'非翻译区 (UTR) 在体内形成高度折叠的结构，通过调节 microRNA 活性来影响基因表达。此外，动态 3'-UTR 结构包含 RNA 衰变元件，如调控元件在 nanog 和 ccna1 中，这两个基因编码关键的母体因子，协调母体到合子的转变。这些结果揭示了 RNA 结构动力学在基因调控程序中的核心作用。
