The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control
The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control
复制标题
DOI：
10.1091/mbc.e07-12-1264
复制
发表时间：
2008-09-01
影响因子：
3.3
通讯作者：
Tarn, Woan-Yuh
中科院分区：
文献类型：
--
作者：
Lai, Ming-Chih;Lee, Yan-Hwa Wu;Tarn, Woan-Yuh
核输出的基因与转录、核基因的加工以及随后细胞质中的成熟密切相关。TIP相关蛋白(TIP-Association Protein，TAP)是核内主要的信使核糖核酸输出受体，与多种参与信使核糖核酸表达的因子协同作用。我们筛选了与TAP相关的蛋白质因子，并确定了几个候选因子，包括RNA解旋酶DDX3。我们证明了DDX3与TAP直接相互作用，并且它与TAP以及核糖核蛋白复合体的结合可能发生在细胞核中。TAP的耗尽导致了DDX3的核积累，这表明DDX3至少部分地与信使核糖核蛋白一起通过TAP介导的途径输出到细胞质中。此外，观察到DDX3在细胞应激条件下瞬时定位于细胞质应激颗粒中，这表明DDX3在翻译调控中发挥了作用。事实上，DDX3与翻译起始复合体有关。然而，DDX3可能对一般的mRNA翻译并不是关键的，而是可能促进含有一个长的或结构化的5‘非翻译区的mRNAs的有效翻译。鉴于DDX3 RNA解旋酶的活性对于其参与翻译是必不可少的，我们认为DDX3在核糖体扫描过程中通过解析mRNAs中5‘-非翻译区的二级结构来促进翻译。
Nuclear export of mRNA is tightly linked to transcription, nuclear mRNA processing, and subsequent maturation in the cytoplasm. Tip-associated protein (TAP) is the major nuclear mRNA export receptor, and it acts coordinately with various factors involved in mRNA expression. We screened for protein factors that associate with TAP and identified several candidates, including RNA helicase DDX3. We demonstrate that DDX3 directly interacts with TAP and that its association with TAP as well as mRNA ribonucleoprotein complexes may occur in the nucleus. Depletion of TAP resulted in nuclear accumulation of DDX3, suggesting that DDX3 is, at least in part, exported along with messenger ribonucleoproteins to the cytoplasm via the TAP-mediated pathway. Moreover, the observation that DDX3 localizes transiently in cytoplasmic stress granules under cell stress conditions suggests a role for DDX3 in translational control. Indeed, DDX3 associates with translation initiation complexes. However, DDX3 is probably not critical for general mRNA translation but may instead promote efficient translation of mRNAs containing a long or structured 5' untranslated region. Given that the DDX3 RNA helicase activity is essential for its involvement in translation, we suggest that DDX3 facilitates translation by resolving secondary structures of the 5'-untranslated region in mRNAs during ribosome scanning.