Hatfield S D, Shcherbata H R, Fischer K A, Nakahara K, Carthew R W, Ruohola-Baker H
Department of Biochemistry, University of Washington, J591, HSB, Seattle, Washington 98195-7350, USA.
Nature. 2005 Jun 16;435(7044):974-8. doi: 10.1038/nature03816. Epub 2005 Jun 8.
One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition.
干细胞的关键特性之一是，在大多数细胞处于静止状态的环境中，它们能够长时间进行分裂。因此，干细胞生物学中的一个关键问题是，干细胞如何逃避细胞分裂停止信号。在此，我们报告了微小RNA（miRNA）途径对于果蝇生殖系干细胞（GSC）分裂的适当控制的必要性。对dicer-1（dcr-1）突变的GSC进行分析，dicer-1是miRNA生物合成所必需的双链核糖核酸酶III，结果显示生殖系囊肿产生率显著降低。这些dcr-1突变的GSC表现出正常的特性，但在细胞周期控制方面存在缺陷。基于细胞周期标记和遗传相互作用，我们得出结论，dcr-1突变的GSC在G1期到S期的转换中延迟，这依赖于细胞周期蛋白依赖性激酶抑制剂Dacapo，这表明miRNA是干细胞绕过正常G1/S检查点所必需的。因此，miRNA途径可能是使干细胞对通常在G1/S转换时停止细胞周期的环境信号不敏感的机制的一部分。
