Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon
{"title":"成熟 microRNA 结合蛋白 QKI 可抑制细胞外 microRNA let-7b 的释放。","authors":"Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon","doi":"10.1242/jcs.261575","DOIUrl":null,"url":null,"abstract":"<p><p>Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs. Among those proteins, the RBP quaking (QKI) inhibits extracellular release of the mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as AUF1 (also known as hnRNPD) and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates Toll-like receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in the mouse cortex. Thus, this study reveals the contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574364/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.\",\"authors\":\"Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon\",\"doi\":\"10.1242/jcs.261575\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs. Among those proteins, the RBP quaking (QKI) inhibits extracellular release of the mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as AUF1 (also known as hnRNPD) and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates Toll-like receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in the mouse cortex. Thus, this study reveals the contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release.</p>\",\"PeriodicalId\":15227,\"journal\":{\"name\":\"Journal of cell science\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574364/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of cell science\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1242/jcs.261575\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cell science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/jcs.261575","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.
Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs. Among those proteins, the RBP quaking (QKI) inhibits extracellular release of the mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as AUF1 (also known as hnRNPD) and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates Toll-like receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in the mouse cortex. Thus, this study reveals the contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release.