Hüttelmaier Stefan, Zenklusen Daniel, Lederer Marcell, Dictenberg Jason, Lorenz Mike, Meng Xiuhua, Bassell Gary J, Condeelis John, Singer Robert H
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Nature. 2005 Nov 24;438(7067):512-5. doi: 10.1038/nature04115.
Localization of beta-actin messenger RNA to sites of active actin polymerization modulates cell migration during embryogenesis, differentiation and possibly carcinogenesis. This localization requires the oncofetal protein ZBP1 (Zipcode binding protein 1), which binds to a conserved 54-nucleotide element in the 3'-untranslated region of the beta-actin mRNA known as the 'zipcode'. ZBP1 promotes translocation of the beta-actin transcript to actin-rich protrusions in primary fibroblasts and neurons. It is not known how the ZBP1-RNA complex achieves asymmetric protein sorting by localizing beta-actin mRNA. Here we show that chicken ZBP1 modulates the translation of beta-actin mRNA. ZBP1 associates with the beta-actin transcript in the nucleus and prevents premature translation in the cytoplasm by blocking translation initiation. Translation only occurs when the ZBP1-RNA complex reaches its destination at the periphery of the cell. At the endpoint of mRNA transport, the protein kinase Src promotes translation by phosphorylating a key tyrosine residue in ZBP1 that is required for binding to RNA. These sequential events provide both temporal and spatial control over beta-actin mRNA translation, which is important for cell migration and neurite outgrowth.
β-肌动蛋白信使核糖核酸定位于肌动蛋白活跃聚合的位点，在胚胎发育、分化以及可能的癌变过程中调节细胞迁移。这种定位需要癌胚蛋白ZBP1（邮政编码结合蛋白1），它与β-肌动蛋白信使核糖核酸3'非翻译区中一个保守的54个核苷酸元件结合，该元件被称为“邮政编码”。ZBP1促进β-肌动蛋白转录本转运至原代成纤维细胞和神经元中富含肌动蛋白的突起处。目前尚不清楚ZBP1-RNA复合物如何通过定位β-肌动蛋白信使核糖核酸实现不对称蛋白质分选。在此我们表明，鸡ZBP1调节β-肌动蛋白信使核糖核酸的翻译。ZBP1在细胞核中与β-肌动蛋白转录本结合，并通过阻断翻译起始来防止细胞质中的过早翻译。只有当ZBP1-RNA复合物到达细胞周边的目的地时才会发生翻译。在信使核糖核酸转运的终点，蛋白激酶Src通过磷酸化ZBP1中与RNA结合所需的一个关键酪氨酸残基来促进翻译。这些连续事件对β-肌动蛋白信使核糖核酸的翻译提供了时间和空间上的控制，这对细胞迁移和神经突生长很重要。
