ELAVL4 encoded RNA binding protein HuD controls skin cellular senescence through CDKN1A

Cellular senescence is described as a stable cell cycle arrest together with secretion of senescence-associated secretory phenotype (SASP) factors. Chronic accumulation of senescent cells in tissues has been revealed to be deleterious as it favors aging and a majority of age-related diseases. Interestingly, the recent discovery of senolytics prompted us to identify more specific senescence markers and to study its internal mechanisms. The ELAVL4 encoded RNA binding protein HuD has been shown to be implicated in some age-associated disorders and skin aging. However, little is known about the regulation of skin cellular senescence by ELAVL4. Here, in this study, we demonstrated that ELVAL4 was upregulated during therapy-induced senescence (TIS). In addition, ELVAL4 knockdown partially delayed the skin cellular senescence and SASP secretion triggered by doxorubicin. Moreover, stabilization of HuD by folic acid (FA) induced a skin cellular senescence phenotype through activating CDKN1A. Altogether, these data indicated that the ELAVL4 encoded HuD controls skin cellular senescence through regulating CDKN1A and thus identified ELAVL4 as a novel skin cellular senescence regulator.