Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation.

Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation.
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DOI:
10.1038/ng.250
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发表时间:
2008-12
期刊:
影响因子:
30.8
通讯作者:
Blelloch, Robert
Blelloch, Robert
中科院分区:
生物学1区
文献类型:
--
作者:
Wang, Yangming;Baskerville, Scott;Shenoy, Archana;Babiarz, Joshua E.;Baehner, Lauren;Blelloch, Robert

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Dgcr 8敲除的胚胎干(ES)细胞缺乏微处理器活性,因此缺乏所有典型的microRNA(miRNA)。这些细胞增殖缓慢,并积累在细胞周期的G1期。在这里,通过在Dgcr 8敲除ES细胞的背景下筛选单个miRNAs的综合文库,我们报告了多个ES细胞特异性miRNAs,miR-290家族的成员,挽救了ES细胞增殖缺陷。此外,拯救的细胞不再在细胞周期的G1期积累。这些miRNAs通过抑制G1/S转换的几个关键调节因子发挥作用。这些结果表明,通过miRNA的转录后调节促进ES细胞周期的G1/S转换,使其能够快速增殖。此外,我们的筛选策略提供了一种替代和强大的方法来揭示单个miRNA在生物过程中的作用,因为它克服了miRNA系统中冗余和饱和的常见问题。
Dgcr8 knockout embryonic stem (ES) cells lack microprocessor activity and hence all canonical microRNAs (miRNAs). These cells proliferate slowly and accumulate in G1 phase of the cell cycle. Here, by screening a comprehensive library of individual miRNAs in the background of the Dgcr8 knockout ES cells, we report that multiple ES cell-specific miRNAs, members of the miR-290 family, rescue the ES cell proliferation defect. Furthermore, rescued cells no longer accumulate in the G1 phase of the cell cycle. These miRNAs function by suppressing several key regulators of the G1/S transition. These results show that post-transcriptional regulation by miRNAs promotes the G1/S transition of the ES cell cycle enabling their rapid proliferation. Furthermore, our screening strategy provides an alternative and powerful approach for uncovering the role of individual miRNAs in biological processes as it overcomes the common problem of redundancy and saturation in the miRNA system.
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