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CNOT1 is involved in TTP‑mediated ICAM‑1 and IL‑8 mRNA decay
Jia-Xin Shi1, Jia-Shu Li1, Rong Hu1
1Department of Respiratory Medicine, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu 222002, P.R. China.
Molecular Medicine Reports
|June 30, 2018
Summary
Carbon catabolite repressor protein 4-negative on TATA (CNOT1) complex subunit 1 acts as a scaffold. CNOT1 is crucial for tristetraprolin-mediated decay of ICAM-1 and IL-8 mRNA.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cell Biology
Background:
- Tristetraprolin (TTP) recruits CNOT7 to degrade ICAM-1 and IL-8 mRNA.
- TTP, CNOT7, and CNOT1 form a complex in HPMECs.
- The role of CNOT1 in TTP-mediated mRNA decay was previously unclear.
Purpose of the Study:
- To investigate the role of CNOT1 in TTP-mediated decay of ICAM-1 and IL-8 mRNA.
- To elucidate the mechanism of CNOT1 involvement in mRNA regulation.
Main Methods:
- CNOT1 knockdown experiments.
- mRNA stabilization and protein expression analysis.
- Immunofluorescence and co-immunoprecipitation assays.
Main Results:
- CNOT1 knockdown stabilized ICAM-1 and IL-8 mRNA and increased protein levels.
- CNOT1, CNOT7, and TTP co-localize in the cytoplasm.
- CNOT1 silencing disrupted CNOT7 and TTP co-immunoprecipitation, indicating CNOT1's scaffolding role.
Conclusions:
- CNOT1 serves as a platform for TTP and CNOT7 recruitment.
- CNOT1 is essential for TTP-mediated decay of ICAM-1 and IL-8 mRNA.
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