Details

Autor(en) / Beteiligte

• Min, Kyung-Won
• Jo, Myung Hyun
• Song, Minseok
• Lee, Ji Won
• Shim, Min Ji
• Kim, Kyungmin
• Park, Hyun Bong
• Ha, Shinwon
• Mun, Hyejin
• Polash, Ahsan
• Hafner, Markus
• Cho, Jung-Hyun
• Kim, Dongsan
• Jeong, Ji-Hoon
• Ko, Seungbeom
• Hohng, Sungchul
• Kang, Sung-Ung
• Yoon, Je-Hyun

Titel

Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing

Ist Teil von

• RNA biology, 2024, Vol.21 (1), p.1-15

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI regulates miRNA-mediated gene silencing at multiple steps, and collectively serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. This finding indicates that QKI is a complementary factor in miRNA-mediated mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows the assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI overexpression suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumour suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.