PLoS Genetics (Feb 2021)

RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes.

  • Qingtang Shen,
  • Yifan E Wang,
  • Mathew Truong,
  • Kohila Mahadevan,
  • Jingze J Wu,
  • Hui Zhang,
  • Jiawei Li,
  • Harrison W Smith,
  • Craig A Smibert,
  • Alexander F Palazzo

DOI
https://doi.org/10.1371/journal.pgen.1009378
Journal volume & issue
Vol. 17, no. 2
p. e1009378

Abstract

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Mutations in RanBP2 (also known as Nup358), one of the main components of the cytoplasmic filaments of the nuclear pore complex, contribute to the overproduction of acute necrotizing encephalopathy (ANE1)-associated cytokines. Here we report that RanBP2 represses the translation of the interleukin 6 (IL6) mRNA, which encodes a cytokine that is aberrantly up-regulated in ANE1. Our data indicates that soon after its production, the IL6 messenger ribonucleoprotein (mRNP) recruits Argonautes bound to let-7 microRNA. After this mRNP is exported to the cytosol, RanBP2 sumoylates mRNP-associated Argonautes, thereby stabilizing them and enforcing mRNA silencing. Collectively, these results support a model whereby RanBP2 promotes an mRNP remodelling event that is critical for the miRNA-mediated suppression of clinically relevant mRNAs, such as IL6.