RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes

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...

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Veröffentlicht in:PLoS genetics 2021-02, Vol.17 (2), p.e1009378-e1009378
Hauptverfasser: Shen, Qingtang, Wang, Yifan E, Truong, Mathew, Mahadevan, Kohila, Wu, Jingze J, Zhang, Hui, Li, Jiawei, Smith, Harrison W, Smibert, Craig A, Palazzo, Alexander F
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container_title PLoS genetics
container_volume 17
creator Shen, Qingtang
Wang, Yifan E
Truong, Mathew
Mahadevan, Kohila
Wu, Jingze J
Zhang, Hui
Li, Jiawei
Smith, Harrison W
Smibert, Craig A
Palazzo, Alexander F
description 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.
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subjects Adenine
Binding sites
Biology and life sciences
Coding
Cytokines
Cytoplasm
Encephalopathy
Experiments
Hydrophobicity
Infections
Medicine and Health Sciences
MicroRNAs
miRNA
Missense mutation
Mutation
Neural coding
Neurological diseases
Open reading frames
Pediatrics
Plasmids
Proteins
Ran-binding protein
Research and Analysis Methods
Risk factors
Translation
Zinc finger
Zinc finger proteins
title RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes
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