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Formation of mRNPs and mRNA localization

mRNP 的形成和 mRNA 定位

基本信息

批准号：
15590088
负责人：
MATSUMOTO Ken
金额：
$ 2.24万
依托单位：
RIKEN
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590088/
关键词：
mRNP Y-box protein Translational control Y-ボックス蛋白質 mRNAの局在 RNA結合蛋白質

项目摘要

In eukaryotic cells, substrates of the translational machinery are messenger ribonucleoproteins (mRNPs), complexes of mRNAs with a specific set of proteins. In animal female and male germ cells, mRNAs that are required for future development of embryos and sperm are stored as translationally inactive mRNPs in the cytoplasm. The Y-box proteins are major components of cytoplasmic mRNPs in higher eukaryotic cells. Y-box proteins regulate translation in a dose-dependent manner. It has been proposed that Y-box proteins are likely responsible for packaging of mRNAs into mRNPs. Consistent with this proposition, the in vitro reconstitution of mRNA-Y-box protein complexes resulted in compact mRNPs. In such mRNPs, translation of the mRNA was repressed. Conversely, cells in which the genes encoding the Y-box protein YB-1 were disrupted showed slow-growth phenotype and, in these cells, global translation was repressed. Thus, regulation of the availability of Y-box proteins in cells would have an influence on mRNA metabolism and the control of cell proliferation. One of the ways with which Y-box proteins are released from mRNA is to interact with an acidic protein(s). Indeed, our analysis of YB-1-containing complexes isolated from cells identified a Y-box protein-associated acidic protein (YBAP1). The specific association of the YB-1 tail domain with YBAP1 results in the release of YB-1 from the reconstituted YB-1-mRNA complexes. YBAP1 added into the in vitro translation system relieved the translational repression by YB-1. Moreover, we found that in ascidian oocytes the Y-box protein colocalized and associated with Cipem and Ci-macho mRNAs, which are localized at the posterior end of the embryo at the cleavage stage. Our results suggest that associating with the Y-box proteins contributes to the translational control of the localized mRNAs in eggs and embryos.

在真核细胞中，翻译机制的底物是信使核糖核蛋白(MRNPs)，即mRNAs与一组特定蛋白质的复合体。在动物雌性和雄性生殖细胞中，未来胚胎和精子发育所需的mRNAs作为翻译不活跃的mRNPs储存在细胞质中。Y-box蛋白是高等真核细胞胞质mRNPs的主要成分。Y-box蛋白以剂量依赖的方式调节翻译。有人提出，Y-box蛋白可能负责将mRNAs包装成mRNPs。与这一命题一致，mRNA-Y-box蛋白复合体的体外重组导致了致密的mRNPs。在这些mRNPs中，mRNA的翻译被抑制。相反，编码Y-box蛋白YB-1的基因被破坏的细胞表现出生长缓慢的表型，并且在这些细胞中，整体翻译受到抑制。因此，调节Y-box蛋白在细胞中的可获得性将对mRNA的代谢和细胞增殖的控制产生影响。Y-box蛋白从信使核糖核酸释放的方式之一是与酸性蛋白相互作用(S)。事实上，我们对从细胞中分离的含有YB-1的复合体的分析确定了一种Y-box蛋白相关酸性蛋白(YBAP1)。YB-1尾部结构域与YBAP1的特异性结合导致重组的YB-1-mRNA复合体释放YB-1。在体外翻译系统中加入YBAP1可以缓解YB-1对翻译的抑制。此外，我们还发现，在海鞘卵母细胞中，Y-box蛋白与Cipem和ci-macho mRNAs共定位，并与Cipem和ci-macho mRNAs共存，这两个mRNAs位于卵裂期胚胎的后端。我们的结果表明，与Y-box蛋白结合有助于在鸡蛋和胚胎中对定位的mRNAs进行翻译控制。