Posttranscriptional control of the stem cell and neurogenic programs by the nonsense-mediated RNA decay pathway.
Posttranscriptional control of the stem cell and neurogenic programs by the nonsense-mediated RNA decay pathway.
复制标题
DOI：
10.1016/j.celrep.2014.01.028
复制
发表时间：
2014-02-27
期刊：
影响因子：
8.8
通讯作者：
Wilkinson MF
中科院分区：
文献类型：
--
作者：
Lou CH;Shao A;Shum EY;Espinoza JL;Huang L;Karam R;Wilkinson MF
决定细胞是否增殖或分化的机制已经经过了严格的审查，但仍知之甚少。在这里，我们报告说，无义介导的 RNA 衰变 (NMD) 途径的核心成分——UPF1——通过促进增殖、未分化的细胞状态在这一决定中发挥着关键作用。 UPF1 的作用部分是通过破坏编码 TGFβ 抑制剂 SMAD7 的 NMD 底物的稳定性，并刺激 TGFβ 信号传导。 UPF1 还促进编码许多其他蛋白质的 mRNA 的衰变，这些蛋白质反对增殖、未分化的细胞状态。当 NMD 被神经表达的 microRNA (miRNA) 下调时，就会触发神经分化。这种 UPF1-miRNA 电路高度保守，并具有充当分子开关的负反馈环。我们的结果表明，NMD RNA 衰变途径与 TGF-β 信号途径协同锁定茎样状态，当收到诱导 NMD 抑制 miRNA 的神经分化信号时，这种细胞状态会稳定逆转。
The mechanisms dictating whether a cell proliferates or differentiates have undergone intense scrutiny but remain poorly understood. Here, we report that a central component in the nonsense-mediated RNA decay (NMD) pathway—UPF1—plays a key role in this decision by promoting the proliferative, undifferentiated cell state. UPF1 acts, in part, by destabilizing the NMD substrate encoding the TGFβ inhibitor, SMAD7, and stimulating TGFβ signaling. UPF1 also promotes the decay of mRNAs encoding many other proteins that oppose the proliferative, undifferentiated cell state. Neural differentiation is triggered when NMD is downregulated by neurally expressed microRNAs (miRNAs). This UPF1-miRNA circuitry is highly conserved and harbors negative feedback loops that act as a molecular switch. Our results suggest that the NMD RNA decay pathway collaborates with the TGF-β signaling pathway to lock-in the stem-like state, a cellular state that is stably reversed when neural differentiation signals that induce NMD-repressive miRNAs are received.
登录
查看更多内容
影响因子：
16
作者：
Huang L;Lou CH;Chan W;Shum EY;Shao A;Stone E;Karam R;Song HW;Wilkinson MF
通讯作者：
Wilkinson MF
影响因子：
5.2
作者：
Krichevsky, Anna M.;Sonntag, Kai-C.;Kosik, Kenneth S.
通讯作者：
Kosik, Kenneth S.
影响因子：
9.2
作者：
Dostie, J;Dreyfuss, G
通讯作者：
Dreyfuss, G
影响因子：
3.9
作者：
Crespo, Marta Vicente;Palacios, Isabel M.
通讯作者：
Palacios, Isabel M.
影响因子：
4.8
作者：
Halder, SK;Beauchamp, RD;Datta, PK
通讯作者：
Datta, PK