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Cell senescence database
General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction

Basic Information

Gene ID

64393

Name

ZMAT3

Synonymous

zinc finger, matrin-type 3;ZMAT3;zinc finger, matrin-type 3

Definition

WIG-1/PAG608 protein|p53 target zinc finger protein|p53-activated gene 608 protein|zinc finger matrin-type protein 3|zinc finger protein WIG-1|zinc finger protein WIG1|zinc finger, matrin type 3

Position

3q26.32

Gene type

protein-coding

Title

Abstract

Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment.

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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