Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks. Wang Jiaxu et al

The distribution, dynamics and function of RNA structures in human development is under-explored. Here, we systematically assayed RNA structural dynamics and its relationship with gene expression, translation and decay during human neurogenesis. We observed that the human ESC transcriptome is globally more structurally accessible than differentiated cells; and undergo extensive RNA structure changes, particularly in the 3’UTR. Additionally, RNA structure changes during differentiation is associated with translation and decay. We observed that RBP and miRNA binding is associated with RNA structural changes during early neuronal differentiation and splicing is associated during later neuronal differentiation. Further, our analysis suggest that RBPs are major factors in structure remodeling and co-regulate additional RBPs and miRNAs through structure. We demonstrated an example of this by showing that PUM2-induced structure changes on LIN28A enable miR-30 binding. This study deepens our understanding of the wide-spread and complex role of RNA-based gene regulation during human development.

人类发育过程中RNA结构的分布、动态变化及其功能尚处于探索阶段。本研究系统性地评估了RNA结构动态变化及其与基因表达、翻译及降解在人类神经发生过程中的关系。我们发现，人类胚胎干细胞（ESC）的转录组在整体上相较于分化细胞拥有更高的结构可及性；并经历了广泛的RNA结构变化，特别是在3'UTR区域。此外，RNA结构变化与分化过程中的翻译及降解相关。我们观察到，RNA结合蛋白（RBP）和miRNA的结合与早期神经分化过程中的RNA结构变化相关，而剪接则与后期神经分化相关。进一步分析表明，RBPs是结构重塑的主要因素，并通过结构协同调节其他RBPs和miRNA。我们通过展示PUM2诱导LIN28A的结构变化从而实现miR-30结合的例子，证明了这一点。本研究加深了我们对于人类发育过程中RNA为基础的基因调控广泛而复杂角色的理解。