The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the β-actin mRNA in a U-rich-element-dependent manner
The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the β-actin mRNA in a U-rich-element-dependent manner
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DOI：
10.1128/mcb.00113-07
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发表时间：
2007-08-01
影响因子：
5.3
通讯作者：
Gallouzi, Imed-Eddine
中科院分区：
文献类型：
--
作者：
Dormoy-Raclet, Virginie;Menard, Isabelle;Gallouzi, Imed-Eddine
β-肌动蛋白的高表达水平是重要的生物学机制所必需的，例如维持细胞形状、生长和运动性。虽然β-肌动蛋白的细胞水平升高与其mRNA的长半衰期直接相关，但导致这种效应的分子机制尚不清楚。在这里，我们表明，RNA结合蛋白HuR稳定β-肌动蛋白mRNA与尿苷丰富的元素在其3'非翻译区。使用RNA干扰敲低HeLa细胞中HuR的表达，我们证明HuR在β-肌动蛋白mRNA的稳定性中起重要作用，但不在核/胞质分布中。HeLa细胞中HuR的缺失改变了关键的基于β-肌动蛋白的细胞骨架功能，如细胞粘附、迁移和侵袭，这些缺陷与肌动蛋白应力纤维网络的丢失相关。总之，我们的数据确定，涉及HuR介导的β-肌动蛋白mRNA稳定的转录后事件可能是负责维持细胞完整性的调节机制的一部分，这是避免转化和肿瘤形成的先决条件。
A high expression level of the beta-actin protein is required for important biological mechanisms, such as maintaining cell shape, growth, and motility. Although the elevated cellular level of the beta-actin protein is directly linked to the long half-life of its mRNA, the molecular mechanisms responsible for this effect are unknown. Here we show that the RNA-binding protein HuR stabilizes the beta-actin mRNA by associating with a uridine-rich element within its 3' untranslated region. Using RNA interference to knock down the expression of HuR in HeLa cells, we demonstrate that HuR plays an important role in the stabilization but not in the nuclear/cytoplasmic distribution of the beta-actin mRNA. HuR depletion in HeLa cells alters key beta-actin-based cytoskeleton functions, such as cell adhesion, migration, and invasion, and these defects correlate with a loss of the actin stress fiber network. Together our data establish that the posttranscriptional event involving HuR-mediated beta-actin mRNA stabilization could be a part of the regulatory mechanisms responsible for maintaining cell integrity, which is a prerequisite for avoiding transformation and tumor formation.