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The translational landscape of ground state pluripotency.
Nature Communications ( IF 16.6 ) Pub Date : 2020-04-01 , DOI: 10.1038/s41467-020-15449-9
Yaser Atlasi 1, 2 , Seyed Mehdi Jafarnejad 2 , Christos G Gkogkas 3 , Michiel Vermeulen 4 , Nahum Sonenberg 5 , Hendrik G Stunnenberg 1, 6
Affiliation  

Translational control plays a central role in regulation of gene expression and can lead to significant divergence between mRNA- and protein-abundance. Here, we used genome-wide approaches combined with time-course analysis to measure the mRNA-abundance, mRNA-translation rate and protein expression during the transition of naïve-to-primed mouse embryonic stem cells (ESCs). We find that the ground state ESCs cultured with GSK3-, MEK-inhibitors and LIF (2iL) display higher ribosome density on a selective set of mRNAs. This set of mRNAs undergo strong translational buffering to maintain stable protein expression levels in 2iL-ESCs. Importantly, we show that the global alteration of cellular proteome during the transition of naïve-to-primed pluripotency is largely accompanied by transcriptional rewiring. Thus, we provide a comprehensive and detailed overview of the global changes in gene expression in different states of ESCs and dissect the relative contributions of mRNA-transcription, translation and regulation of protein stability in controlling protein abundance.



中文翻译:

基态多能性的平移景观。

翻译控制在基因表达的调节中起着核心作用,并可能导致mRNA和蛋白质丰度之间的显着差异。在这里,我们使用了全基因组方法与时程分析相结合,以测量从幼稚到初免的小鼠胚胎干细胞(ESC)过渡过程中的mRNA丰度,mRNA翻译率和蛋白质表达。我们发现,与GSK3,MEK抑制剂和LIF(2iL)培养的基态ESC在一组选择性的mRNA上显示出更高的核糖体密度。这套mRNA经历强大的翻译缓冲,以维持2iL-ESCs中稳定的蛋白质表达水平。重要的是,我们表明,从幼稚到原始的多能性的过渡过程中,细胞蛋白质组的整体变化在很大程度上伴随着转录重新连接。从而,

更新日期:2020-04-24
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