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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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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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.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1009378</identifier><identifier>PMID: 33600493</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PLoS genetics, 2021-02, Vol.17 (2), p.e1009378-e1009378</ispartof><rights>2021 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Shen et al 2021 Shen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-5a7826c61da426275ae51d5784657fe4223bd2ece6858c406f073bfcb5c6e4c63</citedby><cites>FETCH-LOGICAL-c526t-5a7826c61da426275ae51d5784657fe4223bd2ece6858c406f073bfcb5c6e4c63</cites><orcidid>0000-0002-2680-0570 ; 0000-0002-0981-8058 ; 0000-0002-9125-7893 ; 0000-0002-9700-1995 ; 0000-0001-6930-2224</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924746/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924746/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33600493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Matunis, Michael J.</contributor><creatorcontrib>Shen, Qingtang</creatorcontrib><creatorcontrib>Wang, Yifan E</creatorcontrib><creatorcontrib>Truong, Mathew</creatorcontrib><creatorcontrib>Mahadevan, Kohila</creatorcontrib><creatorcontrib>Wu, Jingze J</creatorcontrib><creatorcontrib>Zhang, Hui</creatorcontrib><creatorcontrib>Li, Jiawei</creatorcontrib><creatorcontrib>Smith, Harrison W</creatorcontrib><creatorcontrib>Smibert, Craig A</creatorcontrib><creatorcontrib>Palazzo, Alexander F</creatorcontrib><title>RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><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.</description><subject>Adenine</subject><subject>Binding sites</subject><subject>Biology and life sciences</subject><subject>Coding</subject><subject>Cytokines</subject><subject>Cytoplasm</subject><subject>Encephalopathy</subject><subject>Experiments</subject><subject>Hydrophobicity</subject><subject>Infections</subject><subject>Medicine and Health Sciences</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Missense mutation</subject><subject>Mutation</subject><subject>Neural coding</subject><subject>Neurological diseases</subject><subject>Open reading frames</subject><subject>Pediatrics</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Ran-binding protein</subject><subject>Research and Analysis Methods</subject><subject>Risk 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J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RanBP2/Nup358 enhances miRNA activity by sumoylating Argonautes</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>17</volume><issue>2</issue><spage>e1009378</spage><epage>e1009378</epage><pages>e1009378-e1009378</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><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. 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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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