Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin Signaling.
Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin Signaling.
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DOI：
10.1016/j.cell.2017.11.023
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发表时间：
2018-01-11
期刊：
影响因子：
64.5
通讯作者：
Hochedlinger K
中科院分区：
文献类型：
--
作者：
Brumbaugh J;Di Stefano B;Wang X;Borkent M;Forouzmand E;Clowers KJ;Ji F;Schwarz BA;Kalocsay M;Elledge SJ;Chen Y;Sadreyev RI;Gygi SP;Hu G;Shi Y;Hochedlinger K
细胞命运转变涉及快速的基因表达变化和整体染色质重塑，但潜在的调控途径仍然不完全清楚。在这里，我们确定了RNA加工因子Nudt 21作为一种新的调节细胞命运的变化，使用转录因子诱导的重编程作为筛选试验。Nudt 21的抑制增强了诱导多能干细胞的产生，促进了向滋养层干细胞的转分化，并损害了骨髓前体细胞和胚胎干细胞的分化，这表明Nudt 21在细胞命运改变中具有更广泛的作用。我们发现，Nudt 21指导获得多能性的细胞中超过1,500个转录本的差异聚腺苷酸化，尽管只有一部分改变了蛋白质水平。值得注意的是，这些蛋白质强烈富集染色质调节剂，并且它们的抑制在重编程期间中和了Nudt 21的作用。总的来说，我们的数据揭示了Nudt 21作为一种新的细胞命运的转录后调节因子，并建立了一个直接的，以前未被重视的联系之间的替代聚腺苷酸化和染色质信号。选择性多聚腺苷酸化对细胞命运决定和多能性发挥转录后控制作用
Cell fate transitions involve rapid gene expression changes and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we identified the RNA-processing factor Nudt21 as a novel regulator of cell fate change using transcription factor induced reprogramming as a screening assay. Suppression of Nudt21 enhanced the generation of induced pluripotent stem cells, facilitated transdifferentiation into trophoblast stem cells, and impaired differentiation of myeloid precursors and embryonic stem cells, suggesting a broader role for Nudt21 in cell fate change. We show that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency, although only a fraction changed protein levels. Remarkably, these proteins were strongly enriched for chromatin regulators and their suppression neutralized the effect of Nudt21 during reprogramming. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling. Alternative polyadenylation exerts post-transcriptional control over cell fate decisions and pluripotency
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.8
作者：
Gaspar-Maia A;Alajem A;Polesso F;Sridharan R;Mason MJ;Heidersbach A;Ramalho-Santos J;McManus MT;Plath K;Meshorer E;Ramalho-Santos M
通讯作者：
Ramalho-Santos M
影响因子：
64.5
作者：
Ang YS;Tsai SY;Lee DF;Monk J;Su J;Ratnakumar K;Ding J;Ge Y;Darr H;Chang B;Wang J;Rendl M;Bernstein E;Schaniel C;Lemischka IR
通讯作者：
Lemischka IR
影响因子：
9.9
作者：
Gupta, Ishaan;Clauder-Muenster, Sandra;Steinmetz, Lars M.
通讯作者：
Steinmetz, Lars M.
DOI：
10.1073/pnas.0900028106
发表时间：
2009-04-28
影响因子：
11.1
作者：
Ji, Zhe;Lee, Ju Youn;Tian, Bin
通讯作者：
Tian, Bin