Modular RNA interactions shape FXR1 condensates involved in mRNA localization and translation

Biomolecular condensates are found throughout a diversity of eukaryotic cell types and cellular compartments, playing roles in various cellular functions. A given protein generally forms functionally and compositionally heterogeneous condensates, but the underlying regulatory mechanisms are unknown. Here, we found that different RNA motifs modulate the formation of heterogeneous mRNA-protein condensates via riboregulation. Fragile X-related 1 (FXR1), an RNA-binding protein interacting with nuclear pores, assembles distinct localized subcellular mRNP condensates linked to cytosolic accumulation of G-quadruplex-containing pluripotent mRNAs and the localized translation of nucleoporin mRNAs at nuclear pores. The diverse locations of FXR1 condensates depend on the unique RNA-protein interaction modules of its two RNA binding domains, and the opposing effects of different RNA motifs on the affinity of FXR1 for nuclear pores. Notably, reduced FXR1 levels and impaired nuclear pore function lead to the nuclear accumulation of transcribed RNAs, facilitating fate transition in human embryonic stem cells. Preventing this decline would result in impaired hESC differentiation.