Faculty, Staff and Student Publications
Publication Date
11-1-2024
Journal
Journal of Cell Science
Abstract
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.
Keywords
MicroRNAs, RNA-Binding Proteins, Animals, Mice, Humans, Extracellular Vesicles, Toll-Like Receptor 7, Mice, Inbred C57BL, Heterogeneous Nuclear Ribonucleoprotein D0, Heterogeneous-Nuclear Ribonucleoprotein D, HEK293 Cells, Cytokines, QKI, AGO2, RNA-binding protein, let-7b, Extracellular vesicular miRNA
DOI
10.1242/jcs.261575
PMID
39308343
PMCID
PMC11574364
PubMedCentral® Posted Date
11-6-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Genetics Commons, Oncology Commons