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

Jiabin Yang1, Zhongyang Chen1, Jiayin He1

  • 1State Key Laboratory of Common Mechanism Research for Major Diseases, Key Laboratory of RNA and Hematopoietic Regulation, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

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RNA motifs regulate mRNA-protein condensates through riboregulation. Fragile X-related 1 (FXR1) protein localization to nuclear pores influences condensate formation, impacting human embryonic stem cell differentiation.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Biomolecular condensates are crucial for cellular functions across eukaryotes.
  • The mechanisms governing the heterogeneity and regulation of protein-RNA condensates remain largely unknown.
  • RNA-binding proteins play key roles in organizing these condensates.

Purpose of the Study:

  • To investigate the role of RNA motifs in modulating mRNA-protein condensate formation.
  • To elucidate the regulatory mechanisms of Fragile X-related 1 (FXR1) condensate localization and function.
  • To understand the impact of FXR1 and nuclear pore function on stem cell fate and differentiation.

Main Methods:

  • Analysis of mRNA-protein condensate formation and localization.
  • Investigation of RNA-protein interactions using Fragile X-related 1 (FXR1).
  • Study of G-quadruplex-containing and nucleoporin mRNAs in condensate assembly.
  • Assessment of nuclear pore function and RNA localization in human embryonic stem cells (hESCs).

Main Results:

  • Specific RNA motifs were found to modulate mRNA-protein condensate formation via riboregulation.
  • FXR1 assembles distinct mRNP condensates at nuclear pores, influenced by RNA motifs and its binding domains.
  • FXR1 condensate localization affects cytosolic accumulation of pluripotent mRNAs and nucleoporin mRNA translation.
  • Reduced FXR1 levels and impaired nuclear pore function cause nuclear RNA accumulation, promoting hESC fate transition.

Conclusions:

  • RNA motifs are key regulators of heterogeneous mRNA-protein condensate formation.
  • FXR1's interaction with nuclear pores and specific RNA motifs dictates condensate localization and function.
  • FXR1 and nuclear pore integrity are essential for proper RNA management during human embryonic stem cell differentiation.