Regulation of eIF4E guides a unique translational program to control erythroid maturation.

Regulation of eIF4E guides a unique translational program to control erythroid maturation.
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DOI:
10.1126/sciadv.add3942
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发表时间:
2022-12-23
期刊:
影响因子:
13.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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翻译控制在平衡造血前体和分化中是必不可少的;然而,对该程序的机制知之甚少。我们发现,主要帽结合蛋白eIF 4 E的活性出乎意料地在整个红细胞生成中以动态的方式调节,其与全球蛋白质合成速率解偶联。此外,eIF 4 E活性指导红系成熟,并且增加的eIF 4 E表达使细胞维持在与驱动PTPN 6和Igf 2bp 1表达的翻译程序相关的早期红系状态。5′端非翻译区富含胞嘧啶的基序对eIF 4 E介导的翻译特异性很重要。因此,通过eIF 4 E维持早期红系状态所必需的关键靶基因的选择性翻译突出了造血前体在需要时快速引发红细胞生成成熟的独特机制。eIF 4 E指导静止血液前体中特异性基因表达的独特机制,以保持早期的未成熟状态。
Translation control is essential in balancing hematopoietic precursors and differentiation; however, the mechanisms underlying this program are poorly understood. We found that the activity of the major cap-binding protein eIF4E is unexpectedly regulated in a dynamic manner throughout erythropoiesis that is uncoupled from global protein synthesis rates. Moreover, eIF4E activity directs erythroid maturation, and increased eIF4E expression maintains cells in an early erythroid state associated with a translation program driving the expression of PTPN6 and Igf2bp1. A cytosine-enriched motif in the 5′ untranslated region is important for eIF4E-mediated translation specificity. Therefore, selective translation of key target genes necessary for the maintenance of early erythroid states by eIF4E highlights a unique mechanism used by hematopoietic precursors to rapidly elicit erythropoietic maturation upon need. eIF4E guides a unique mechanism of specific gene expression in quiescent blood precursors to retain early, immature states.
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