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首页> 外文期刊>Molecular cell >Coupled mRNA Stabilization and Translational Silencing of Cyclooxygenase-2 by a Novel RNA Binding Protein, CUGBP2.
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Coupled mRNA Stabilization and Translational Silencing of Cyclooxygenase-2 by a Novel RNA Binding Protein, CUGBP2.

机译：耦合的mRNA稳定和环氧合酶-2的新型RNA结合蛋白CUGBP2的翻译沉默。

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摘要

Cyclooxygenase-2 (COX-2) expression is translationally silenced in epithelial cells undergoing radiation-induced apoptosis. CUGBP2, a predominantly nuclear protein, is also rapidly induced in response to radiation and translocates to the cytoplasm. Antisense-mediated suppression of CUGBP2 renders radioprotection through a COX-2-dependent prostaglandin pathway, providing an in vivo demonstration of translation inhibition activity for CUGBP2. CUGBP2 binds to two sets of AU-rich sequences (AREs) located within the first sixty nucleotides of the COX-2 3' untranslated region (3'UTR). Upon binding, CUGBP2 stabilizes a chimeric luciferase-COX-2 3'UTR mRNA but inhibits its translation. These findings identify a novel paradigm for RNA binding proteins in facilitating opposing functions of mRNA stability and translation inhibition and reveal a mechanism for inhibiting COX-2 expression in cancer cells.
机译：在经历辐射诱导的凋亡的上皮细胞中，环氧合酶2（COX-2）的表达被翻译沉默。 CUGBP2，一种主要的核蛋白，也能响应辐射而快速诱导并转移到细胞质中。反义介导的CUGBP2抑制作用通过依赖COX-2的前列腺素途径提供放射防护，在体内证明了CUGBP2的翻译抑制活性。 CUGBP2与位于COX-2 3'非翻译区（3'UTR）的前60个核苷酸内的两组富含AU的序列（ARE）结合。结合后，CUGBP2使嵌合荧光素酶-COX-2 3'UTR mRNA稳定，但抑制其翻译。这些发现确定了一种RNA结合蛋白的新型范例，可促进mRNA稳定性和翻译抑制的相反功能，并揭示了抑制癌细胞中COX-2表达的机制。

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