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红细胞生成中的翻译调控及失调。

Translational regulation and deregulation in erythropoiesis.

机构信息

Laboratory of Molecular Hematopoiesis, Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Crete, Greece; Graduate Program in Molecular Biology and Biomedicine, Department of Biology, University of Crete, Heraklion, Crete, Greece.

Laboratory of Molecular Hematopoiesis, Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Crete, Greece.

出版信息

Exp Hematol. 2019 Jul;75:11-20. doi: 10.1016/j.exphem.2019.05.004. Epub 2019 May 30.

Abstract

Translational regulation plays a critical role in erythropoiesis, as it reflects the translational needs of enucleated mature erythroid cells in the absence of transcription and the large translational demands of balanced globin chain synthesis during erythroid maturation. In addition, red blood cells need to respond quickly to changes in their environment and the demands of the organism. Translational regulation occurs at several levels in erythroid cells, including the differential utilization of upstream open reading frames during differentiation and in response to signaling and the employment of RNA-binding proteins in an erythroid cell-specific fashion. Translation initiation is a critical juncture for translational regulation in response to environmental signals such as heme and iron availability, whereas regulatory mechanisms for ribosome recycling are consistent with recent observations highlighting the importance of maintaining adequate ribosome levels in differentiating erythroid cells. Translational deregulation in erythroid cells leads to disease associated with ineffective erythropoiesis, further highlighting the pivotal role translational regulation in erythropoiesis plays in human physiology and homeostasis. Overall, erythropoiesis has served as a unique model that has provided invaluable insight into translational regulation.

摘要

翻译调节在红细胞生成中起着关键作用,因为它反映了去核成熟红细胞在没有转录的情况下的翻译需求,以及红细胞成熟过程中平衡珠蛋白链合成的大量翻译需求。此外,红细胞需要快速响应其环境和机体的需求的变化。在红细胞中,翻译调节发生在几个水平上,包括在分化过程中以及响应信号时对上游开放阅读框的差异利用,以及以红细胞特异性方式使用 RNA 结合蛋白。翻译起始是响应环境信号(如血红素和铁的可用性)进行翻译调节的关键环节,而核糖体回收的调节机制与最近的观察结果一致,这些观察结果强调了在分化的红细胞中维持足够的核糖体水平的重要性。红细胞中的翻译失调会导致与无效红细胞生成相关的疾病,这进一步突出了翻译调节在红细胞生成中的关键作用在人体生理学和动态平衡中。总的来说,红细胞生成一直是一个独特的模型,为翻译调节提供了宝贵的见解。

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