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XPO5 promotes primary miRNA processing independently of RanGTP

Author

Listed:
  • Jingjing Wang

    (University of Colorado Boulder)

  • Jerome E. Lee

    (University of Colorado Boulder
    ArcherDX)

  • Kent Riemondy

    (University of Colorado Boulder
    University of Colorado School of Medicine)

  • Yang Yu

    (Memorial Sloan Kettering Cancer Center)

  • Steven M. Marquez

    (University of Colorado Boulder)

  • Eric C. Lai

    (Memorial Sloan Kettering Cancer Center)

  • Rui Yi

    (University of Colorado Boulder)

Abstract

XPO5 mediates nuclear export of miRNA precursors in a RanGTP-dependent manner. However, XPO5-associated RNA species have not been determined globally and it is unclear whether XPO5 has any additional functions other than nuclear export. Here we show XPO5 pervasively binds to double-stranded RNA regions found in some clustered primary miRNA precursors and many cellular RNAs. Surprisingly, the binding of XPO5 to pri-miRNAs such as mir-17~92 and mir-15b~16-2 and highly structured RNAs such as vault RNAs is RanGTP-independent. Importantly, XPO5 enhances the processing efficiency of pri-mir-19a and mir-15b~16-2 by the DROSHA/DGCR8 microprocessor. Genetic deletion of XPO5 compromises the biogenesis of most miRNAs and leads to severe defects during mouse embryonic development and skin morphogenesis. This study reveals an unexpected function of XPO5 for recognizing and facilitating the nuclear cleavage of clustered pri-miRNAs, identifies numerous cellular RNAs bound by XPO5, and demonstrates physiological functions of XPO5 in mouse development.

Suggested Citation

  • Jingjing Wang & Jerome E. Lee & Kent Riemondy & Yang Yu & Steven M. Marquez & Eric C. Lai & Rui Yi, 2020. "XPO5 promotes primary miRNA processing independently of RanGTP," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15598-x
    DOI: 10.1038/s41467-020-15598-x
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