Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks

The distribution, dynamics, and function of RNA structures in human development are under-explored. Here, we systematically assayed RNA structural dynamics and their 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 undergoes extensive RNA structure changes, particularly in the 3′ UTR. Additionally, RNA structure changes during differentiation are 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. Furthermore, our analysis suggests 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 widespread and complex role of RNA-based gene regulation during human development. [Display omitted] •Systematically assayed the role of RNA structures and gene regulation during neurogenesis•The hESC transcriptome is structurally more accessible than that of differentiated cells•Structure changes in differentiation are associated with cellular factors, including RBPs•Demonstrated interplay among RBP, structure, and gene regulation on LIN28A Wang et al. performed global structure mapping, expression, translation, and decay analysis during human neuronal differentiation. They observed that the hESC transcriptome is structurally more accessible than that of differentiated cells, and structure changes are associated with cellular factors, highlighting the complex interplay among RBPs, miRNAs, RNA structure, and gene regulation.