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RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes.

ABSTRACT: 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.

SUBMITTER: Shen Q

PROVIDER: S-EPMC7924746 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes.

Shen Qingtang Q Wang Yifan E YE Truong Mathew M Mahadevan Kohila K Wu Jingze J JJ Zhang Hui H Li Jiawei J Smith Harrison W HW Smibert Craig A CA Palazzo Alexander F AF

PLoS genetics 20210218 2

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 t ...[more]

PMID: 33600493

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