HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation

Colorectal carcinoma RKO cells expressing reduced levels of the RNA‐binding protein HuR (ASHuR) displayed markedly reduced growth. In synchronous RKO populations, HuR was almost exclusively nuclear during early G 1 , increasing in the cytoplasm during late G 1 , S and G 2 . The expression and half‐life of mRNAs encoding cyclins A and B1 similarly increased during S and G 2 , then declined, indicating that mRNA stabilization contributed to their cell cycle‐regulated expression. In gel‐shift assays using radiolabeled cyclin RNA transcripts and RKO protein extracts, only those transcripts corresponding to the 3′‐untranslated regions of cyclins A and B1 formed RNA–protein complexes in a cell cycle‐dependent fashion. HuR directly bound mRNAs encoding cyclins A and B1, as anti‐HuR antibodies supershifted such RNA–protein complexes. Importantly, the expression and half‐life of mRNAs encoding cyclins A and B1 were reduced in ASHuR RKO cells. Our results indicate that HuR may play a critical role in cell proliferation, at least in part by mediating cell cycle‐dependent stabilization of mRNAs encoding cyclins A and B1.