| Abstract: |
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. |
| Keywords: |
controlled study; human cell; cell proliferation; cell cycle; cell cycle s phase; cell division; cell growth; transcription, genetic; cancer cell culture; tumor cells, cultured; colorectal carcinoma; rna binding protein; rna-binding proteins; gene expression regulation, neoplastic; messenger rna; rna, messenger; cytoplasm; cell cycle g2 phase; cyclin b1; proliferation; half life time; cyclin a; cyclin b; cell cycle g1 phase; antigens, surface; protein rna binding; messenger rna synthesis; mrna stability; humans; human; priority journal; article; hur
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