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.
Authors
- Mark T. Bedford (ORCID: https://orcid.org/0000-0002-8899-1050)
- Tilman Heise (ORCID: https://orcid.org/0000-0002-3248-3129)
- Waleed O. Twal (ORCID: https://orcid.org/0000-0002-2888-4544)
- Hainan Lang (ORCID: https://orcid.org/0000-0003-2210-7856)
- Sang‐Ho Kwon (ORCID: https://orcid.org/0000-0001-9074-4641)
- Je‐Hyun Yoon (ORCID: https://orcid.org/0000-0001-7615-8654)
- Seonghyun Ryu (ORCID: https://orcid.org/0000-0002-3384-7852)
- Ted M. Dawson (ORCID: https://orcid.org/0000-0002-6459-0893)
- Sung-Ung Kang (ORCID: https://orcid.org/0000-0002-8393-2588)
- Valina L. Dawson (ORCID: https://orcid.org/0000-0002-2915-3970)
- Cari A. Sagum (ORCID: https://orcid.org/0000-0001-6101-7162)
- Kyung‐Won Min (ORCID: https://orcid.org/0000-0002-8718-3588)
- Jeong Ho Chang (ORCID: https://orcid.org/0000-0002-2126-0317)
- Seungbeom Ko (ORCID: https://orcid.org/0000-0002-8457-3134)
- Clarisse H. Panganiban
- Xin Zhou (ORCID: https://orcid.org/0000-0002-7444-462X)
- Junyang Jung (ORCID: https://orcid.org/0000-0003-3946-5406)
- Seula Shin (ORCID: https://orcid.org/0000-0002-3593-5901)
- Kyoung‐Min Choi
- Kyungmin Kim
- Dongin Kim (ORCID: https://orcid.org/0000-0003-2078-6138)
- Joe Ryan Delaney (ORCID: https://orcid.org/0000-0002-8978-5961)
- Dongsan Kim (ORCID: https://orcid.org/0000-0002-1424-6648)
- Jian Hu (ORCID: https://orcid.org/0000-0001-9760-2013)
- Dong-Chan Kim (ORCID: https://orcid.org/0000-0002-9361-8023)
- Hyejin Mun
- Ji Won Lee (ORCID: https://orcid.org/0009-0009-9951-3685)
- Jung-Hyun Cho (ORCID: https://orcid.org/0000-0002-1952-5611)
- Young‐Kook Kim (ORCID: https://orcid.org/0000-0001-6434-2235)
- Sydney Lewis
- Young Hwa Kim
- Ahmet Eroglu
Institutions
- Gangneung–Wonju National University (KR)
- The University of Texas MD Anderson Cancer Center (US)
- Johns Hopkins University (US)
- Medical University of South Carolina (US)
- Augusta University (US)
- Oklahoma City University (US)
- Johns Hopkins Medicine (US)
- University Hospital Regensburg (DE)
- Kyungpook National University (KR)
- ProQuest (United States) (US)
- Kyung Hee University (KR)
- Chonnam National University Hwasun Hospital (KR)
- University of Oklahoma Health Sciences Center (US)
- University of Regensburg (DE)
- University of Oklahoma (US)
Publication Details
- Journal
- Journal of Cell Science
- Published
- 2024-09-23
- DOI
- https://doi.org/10.1242/jcs.261575
- Citations
- 5
- Primary Topic
- MicroRNA in disease regulation
- Type
- article
- Field-Weighted Citation Impact
- 1.43
Funders
- Memorial Sloan-Kettering Cancer Center
- University of Oklahoma
- University of South Carolina
- Augusta University
- National Research Foundation
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- National Institutes of Health
- Medical College of Georgia, Augusta University
- National Cancer Institute