The mRNA-binding protein Serbp1 as an auxiliary protein associated with mammalian cytoplasmic ribosomes
The mRNA-binding protein Serbp1 as an auxiliary protein associated with mammalian cytoplasmic ribosomes
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DOI：
10.1002/cbf.3350
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发表时间：
2018-08-01
影响因子：
3.6
通讯作者：
Nadano, Daita
中科院分区：
文献类型：
--
作者：
Muto, Akiko;Sugihara, Yoshihiko;Nadano, Daita
虽然转录在基因表达中起着重要的作用，但翻译是最近出现的决定包括哺乳动物在内的高等真核生物细胞中蛋白质组组成和质量的关键步骤。选择性翻译被认为是由细胞质核糖体的结构异质性调节的，包括蛋白质组成和化学修饰的差异。然而，目前对哺乳动物核糖体异质性的了解是有限的。在这里，我们报告哺乳动物Serbp1是一种核糖体相关蛋白。Serbp1基因的翻译产物，包括最长的异构体，定位于核仁和细胞质中。亚细胞分离表明，大部分胞浆中的Serbp1分子通过超速离心法沉淀。蛋白质组学分析证实Serbp1存在于啮齿动物睾丸的胞浆核糖体中。多聚体分析表明，Serbp1作为40s小亚基的一个组成部分，包括在翻译核糖体(多聚体)中。在核糖体亚基解离后，观察到Serbp1与40S亚基的共沉积。Serbp1也包括在人类癌细胞的核糖体中，这可能导致对Serbp1与肿瘤进展之间新出现的联系的机制理解。研究意义：在哺乳动物细胞中，其遗传程序的最终蛋白质输出不仅取决于控制转录，还取决于调节转录后事件。尽管长期以来，mRNA结合蛋白和胞质核糖体一直被认为是转录后调控的中心角色，但它们之间的物理和功能相互作用仍远未完全了解。在这里，我们描述了Serbp1，一种mRNA结合蛋白在细胞内的定位，以及该蛋白在正常细胞和癌细胞中主动翻译核糖体的作用。这些发现为Serbp1在翻译基因调控和肿瘤进展中潜在的分子机制提供了新的线索。
While transcription plays an obviously important role in gene expression, translation has recently been emerged as a key step that defines the composition and quality of the proteome in the cell of higher eukaryotes including mammals. Selective translation is supposed to be regulated by the structural heterogeneity of cytoplasmic ribosomes including differences in protein composition and chemical modifications. However, the current knowledge on the heterogeneity of mammalian ribosomes is limited. Here, we report mammalian Serbp1 as a ribosome-associated protein. The translated products of Serbp1 gene, including the longest isoform, were found to be localized in the nucleolus as well as in the cytoplasm. Subcellular fractionation indicated that most of cytoplasmic Serbp1 molecules were precipitated by ultracentrifugation. Proteomic analysis identified Serbp1 in the cytoplasmic ribosomes of the rodent testis. Polysome profiling suggested that Serbp1, as a component of the small 40S subunit, was included in translating ribosomes (polysomes). Cosedimentation of Serbp1 with the 40S subunit was observed after dissociation of the ribosomal subunits. Serbp1 was also included in the ribosomes of human cancer cells, which may lead to a mechanistic understanding of an emerging link between Serbp1 and tumour progression.Significance of the study: In mammalian cells, the final protein output of their genetic program is determined not only by controlling transcription but also by regulating the posttranscriptional events. Although mRNA-binding proteins and the cytoplasmic ribosome have long been recognized as central players in the posttranscriptional regulation, their physical and functional interactions are still far from a complete understanding. Here, we describe the intracellular localization of Serbp1, an mRNA-binding protein, and the inclusion of this protein in actively translating ribosomes in normal and cancer cells. These findings shed a new light into molecular mechanisms underlying Serbp1 action in translational gene regulation and tumour progression.