HuR regulates p21 mRNA stabilization by UV light

Expression of the cyclin-dependent kinase inhibitor p21 is highly induced b y many stresses, including exposure to short-wavelength UV light (WC), whic h increases p21 mRNA stability. Investigation into the mechanisms underlyin g this stabilization process repealed that proteins present in cytoplasmic lysates of human RKO colorectal carcinoma cells formed complexes with p21 m RNA that were inducible by treatment with UVC and other stress agents. The ubiquitous Elav-type RNA-binding protein HuR was identified within the p21 mRNA-protein complexes, as antibodies recognizing HuR supershifted these co mplexes and revealed HuR-immunoreactive proteins complexing with p21 mRNA o n Western blots. Lowering of endogenous HuR levels through expression of an tisense HuR decreased p21 RNA-protein complexes, greatly reduced the UVC in ducibility and half-life of p21 mRNA, and prevented UVC-mediated induction of luciferase activity in p21 3' untranslated region-containing reporter co nstructs. Our findings indicate that HuR plays a major role in regulating s tress-induced p21 expression by enhancing p21 mRNA stability and that these effects are coupled to HuR's elevated presence in the cytoplasm.