RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes

Shen, Qingtang; Wang, Yifan E.; Mathew, Truong; Mahadevan, Kohila; Wu, Jing Ze; Zhang, Hui; Li, Jiawei; Smith, Harrison W.; Smibert, Craig; Palazzo, Alexander F.

doi:10.1371/journal.pgen.1009378

Cited by 23 publications

(38 citation statements)

References 82 publications

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“…How mutations in RanBP2/Nup358 contribute to disease remains unclear. Our recently published work suggests that RanBP2/Nup358 represses the translation of two ANE1-associated cytokine mRNAs, IL-6 and TNF-α , by sumoylating argonaute proteins thereby enforcing microRNA-mediated silencing ( 240 ). Our data indicate that argonautes initially interact with the IL-6 mRNA in the nucleus, and that after nuclear export, RanBP2-dependent sumoylation stabilizes argonaute binding to the mRNA as part of an mRNP remodeling event.…”

Section: Orthomyxovirusesmentioning

confidence: 99%

Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection

Shen

Wang

Palazzo

2021

Journal of Biological Chemistry

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The nuclear pore complex is the sole gateway connecting the nucleoplasm and cytoplasm. In humans, the nuclear pore complex is one of the largest multiprotein assemblies in the cell, with a molecular mass of ∼110 MDa and consisting of 8 to 64 copies of about 34 different nuclear pore proteins, termed nucleoporins, for a total of 1000 subunits per pore. Trafficking events across the nuclear pore are mediated by nuclear transport receptors and are highly regulated. The nuclear pore complex is also used by several RNA viruses and almost all DNA viruses to access the host cell nucleoplasm for replication. Viruses hijack the nuclear pore complex, and nuclear transport receptors, to access the nucleoplasm where they replicate. In addition, the nuclear pore complex is used by the cell innate immune system, a network of signal transduction pathways that coordinates the first response to foreign invaders, including viruses and other pathogens. Several branches of this response depend on dynamic signaling events that involve the nuclear translocation of downstream signal transducers. Mounting evidence has shown that these signaling cascades, especially those steps that involve nucleocytoplasmic trafficking events, are targeted by viruses so that they can evade the innate immune system. This review summarizes how nuclear pore proteins and nuclear transport receptors contribute to the innate immune response and highlights how viruses manipulate this cellular machinery to favor infection. A comprehensive understanding of nuclear pore proteins in antiviral innate immunity will likely contribute to the development of new antiviral therapeutic strategies.

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Section: Orthomyxovirusesmentioning

confidence: 99%

Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection

Shen

Wang

Palazzo

2021

Journal of Biological Chemistry

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“…Previous studies have shown a role for Nup358 in the miRNA pathway (Sahoo et al, 2017;Shen et al, 2021). Disruption of the miRNA pathway via depletion of GW182 (Pfaff and Meister, 2013) did not affect ERMCS dynamics (Supplementary Fig.…”

Section: Nup358 Depletion Increases the Contacts Between Er And Mitochondriamentioning

confidence: 74%

“…The pathophysiology includes cytokine storm, exemplified by increased levels of pro-inflammatory cytokines such as INF-α and IL-6 in the serum and cerebrospinal fluid of the patients (Levine et al, 2020). Impairment in the miRNA-mediated translation regulation by Nup358 might contribute to the development of ANE-1 (Deshmukh et al, 2021;Shen et al, 2021). However, the functions for AL-associated Nup358 revealed by our studies may provide an additional platform for a better understanding of the pathogenesis of ANE-1.…”

Section: Discussionmentioning

confidence: 99%

Nup358 regulates remodelling of ER-mitochondrial contact sites and autophagy

Kalarikkal

Saikia

Varshney

et al. 2021

Preprint

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The contact sites between ER and mitochondria regulate several cellular processes including inter-organelle lipid transport, calcium homeostasis and autophagy. However, the mechanisms that regulate the dynamics and functions of these contact sites remain unresolved. We show that annulate lamellae (AL), a relatively unexplored subcellular structure representing subdomains of ER enriched with a subset of nucleoporins, are present at ER-mitochondria contact sites (ERMCS). Depletion of one of the AL-resident nucleoporins, Nup358, results in increased contacts between ER and mitochondria. Mechanistically, Nup358 modulates ERMCS dynamics by restricting mTORC2/Akt signalling. Our results suggest that growth factor-mediated remodelling of ERMCS depends on a reciprocal binding of Nup358 and mTOR to the ERMCS tethering complex consisting of VAPB and PTPIP51. Furthermore, Nup358 also interacts with IP3R, an ERMCS-enriched Ca2+ channel, and controls Ca2+ release from the ER. Consequently, depletion of Nup358 leads to elevated cytoplasmic Ca2+ and autophagy via activation of Ca2+/CaMKK2/AMPK axis. Our study thus uncovers a novel role for AL, particularly for Nup358, in regulating mTORC2-mediated ERMCS remodelling and Ca2+-directed autophagy, possibly via independent mechanisms.

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“…Recently, we documented that RanBP2 promotes the microRNA-mediated suppression of ANE1-associated cytokines, such as IL6 and TNF-α [ 30 ]. We found that RanBP2 sumoylates Argonaute proteins thereby promoting their ability to silence the IL6 mRNA.…”

Section: Pathogenesis Of Ane1: Roles Of Ranbp2 In Ane1mentioning

confidence: 99%

“…The formation of the tight RanBP2/SUMO-RanGAP1/Ubc9 complex at the cytoplasmic filaments of the NPC is essential for the SUMO E3-ligase activity of RanBP2 [ 14 ]. Aside from mediating sumoylation, RanBP2 has been implicated in many aspects of cellular processes, including nucleocytoplasmic transport [ 15 , 16 , 17 , 18 ], trafficking of photoreceptors [ 19 , 20 ], glucose metabolism [ 21 ], attachment of microtubules to kinetochores during mitosis [ 22 , 23 , 24 , 25 ], myogenesis [ 26 , 27 ], and mRNA metabolism [ 18 , 28 , 29 ], as well as microRNA-induced silencing [ 30 , 31 , 32 , 33 ]. Beyond the nuclear pore, RanBP2 also appears to form cytosolic aggregates, which may include annulate lamellae and/or some other biomolecular condensates [ 31 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection

Jiang

Wang

Palazzo

et al. 2022

IJMS

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Ran Binding Protein 2 (RanBP2 or Nucleoporin358) is one of the main components of the cytoplasmic filaments of the nuclear pore complex. Mutations in the RANBP2 gene are associated with acute necrotizing encephalopathy type 1 (ANE1), a rare condition where patients experience a sharp rise in cytokine production in response to viral infection and undergo hyperinflammation, seizures, coma, and a high rate of mortality. Despite this, it remains unclear howRanBP2 and its ANE1-associated mutations contribute to pathology. Mounting evidence has shown that RanBP2 interacts with distinct viruses to regulate viral infection. In addition, RanBP2 may regulate innate immune response pathways. This review summarizes recent advances in our understanding of how mutations in RANBP2 contribute to ANE1 and discusses how RanBP2 interacts with distinct viruses and affects viral infection. Recent findings indicate that RanBP2 might be an important therapeutic target, not only in the suppression of ANE1-driven cytokine storms, but also to combat hyperinflammation in response to viral infections.

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RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes

Cited by 23 publications

References 82 publications

Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection

Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection

Nup358 regulates remodelling of ER-mitochondrial contact sites and autophagy

Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection

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