FXR1 dominates mRNA export fate via riboregulation during hESC differentiation

mRNA export is required for its translation into functional protein, facilitated by the interaction between mRNA transporters and nuclear pore complex (NPC). However, only a few mRNA transporters associated with NPC were identified. Here, we comprehensively depicted NPC interactome in human embryonic stem cells (hESCs), from which we identified a series of novel mRNA transporters. Among them, FXR1 functioned as a cytoplasmic mRNA acceptor, promoted the release of G-quadruplex containing mRNA from its export receptor, simultaneously mediated the localization of nucleoporins mRNA on nuclear pore. FXR1 bound G-quadruplex or nucleoporin AGAA RNA via its RGG and KH domain respectively, which in turn weakened or enhanced its binding to nuclear pore, thus resulted in mRNA release or localization. More importantly, the decline of FXR1 and nuclear pore activity helped hESCs to achieve fate transition by impeding the nuclear export of transcribed RNAs, which was required for hESC differentiation.