Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment |
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| Authors: | Bong Cho Kim Hyung Chul Lee Je‐Jung Lee Chang‐Min Choi Dong‐Kwan Kim Jae Cheol Lee Young‐Gyu Ko Jae‐Seon Lee |
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| Affiliation: | 1. Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, , Seoul, Korea;2. School of Life Sciences and Biotechnology, Korea University, , Seoul, Korea;3. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, , Seoul, Korea;4. Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, College of Medicine, University of Ulsan, , Seoul, Korea;5. Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, , Seoul, Korea |
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| Abstract: | Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA‐induced silencing complex (RISC), with target p21 mRNA via binding of the stem‐loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA‐mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA‐mediated gene silencing. In addition, these findings indicate that fine‐tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence. |
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| Keywords: | cellular senescence p21 mRNA stability RISC recruitment RNA‐binding protein Wig1 |
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