Yang Lele, Duan Ranhui, Chen Dongsheng, Wang Jun, Chen Dahua, Jin Peng
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA.
Hum Mol Genet. 2007 Aug 1;16(15):1814-20. doi: 10.1093/hmg/ddm129. Epub 2007 May 21.
Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP). FMRP, which may regulate translation in neurons, associates not only with specific mRNAs and microRNAs (miRNA), but also with components of the miRNA pathway, including Dicer and Argonaute proteins. In Drosophila, dFmr1 is also known to be involved in germ cell and oocyte specification; however, the question of whether dFmr1 is required for controlling the fate of germline stem cells (GSCs) has gone unanswered. Here we show that dFmr1 is required for both GSC maintenance and repressing differentiation. Furthermore, we demonstrate that in Drosophila ovary, dFmr1 protein interacts with Argonaute protein 1 (AGO1), a key component of the miRNA pathway. Thus dFmr1 could modulate the fate of GSCs, likely via the miRNA pathway. Our results provide the first evidence that FMRP might be involved in the regulation of adult stem cells.
脆性X综合征是一种常见的遗传性智力障碍形式，由脆性X智力低下蛋白（FMRP）缺失引起。FMRP可能在神经元中调节翻译，它不仅与特定的信使核糖核酸（mRNA）和微小核糖核酸（miRNA）相关联，还与miRNA途径的组分相关联，包括Dicer和AGO蛋白。在果蝇中，已知dFmr1也参与生殖细胞和卵母细胞的特化；然而，dFmr1是否为控制生殖系干细胞（GSC）的命运所必需这一问题尚未得到解答。在此我们表明，dFmr1对于GSC维持和抑制分化均是必需的。此外，我们证明，在果蝇卵巢中，dFmr1蛋白与miRNA途径的关键组分AGO1相互作用。因此，dFmr1可能通过miRNA途径调节GSC的命运。我们的结果提供了首个证据，表明FMRP可能参与成体干细胞的调控。
