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.