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

Jiabin Yang, Zhongyang Chen, Jiayin He, Binbin Zou, Yanmin Si, Yanni Ma () and Jia Yu ()
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Jiabin Yang: School of Basic Medicine Peking Union Medical College
Zhongyang Chen: School of Basic Medicine Peking Union Medical College
Jiayin He: School of Basic Medicine Peking Union Medical College
Binbin Zou: Chinese Academy of Medical Sciences
Yanmin Si: School of Basic Medicine Peking Union Medical College
Yanni Ma: School of Basic Medicine Peking Union Medical College
Jia Yu: School of Basic Medicine Peking Union Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-63700-y

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