MILI, a PIWI-interacting RNA-binding Protein, Is Required for Germ Line Stem Cell Self-renewal and Appears to Positively Regulate Translation
MILI, a PIWI-interacting RNA-binding Protein, Is Required for Germ Line Stem Cell Self-renewal and Appears to Positively Regulate Translation
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DOI：
10.1074/jbc.m809104200
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发表时间：
2009-03-06
影响因子：
4.8
通讯作者：
Lin, Haifan
中科院分区：
文献类型：
--
作者：
Unhavaithaya, Yingdee;Hao, Yi;Lin, Haifan
Argonaute/PIWI蛋白家族由Argonaute和PIWI亚家族组成。Argonaute在RNA干扰和micro-RNA途径中发挥作用;而PIWI与PIWI相互作用的RNA结合并调节生殖系发育、干细胞维持、表观遗传调节和转座。然而，PIWI在哺乳动物干细胞中的作用尚未得到证实，PIWI介导的分子机制仍然难以捉摸。在这里，我们表明，MILI，小鼠PIWI蛋白，表达在睾丸生殖干细胞，精原细胞和早期精母细胞的细胞质中，在那里它是丰富的类染色体体。MILI对生殖系干细胞的自我更新分裂和分化至关重要，但不影响产后7天生殖系干细胞群体的初始建立。此外，MILI与eIF 3a形成稳定的RNA非依赖性复合物，并与含有eIF 4 E和eIF 4G的m（7）G帽结合复合物结合。在分离的产后7天的生精小管（主要含有生殖系干细胞）中，mili突变对细胞mRNA水平没有影响，但显著降低了蛋白质合成速率。这些观察结果表明，MILI可以积极调节翻译，这种调节是生殖系干细胞自我更新所必需的。
The Argonaute/PIWI protein family consists of Argonaute and PIWI subfamilies. Argonautes function in RNA interference and micro-RNA pathways; whereas PIWIs bind to PIWI-interacting RNAs and regulate germ line development, stem cell maintenance, epigenetic regulation, and transposition. However, the role of PIWIs in mammalian stem cells has not been demonstrated, and molecular mechanisms mediated by PIWIs remain elusive. Here we show that MILI, a murine PIWI protein, is expressed in the cytoplasm of testicular germ line stem cells, spermatogonia, and early spermatocytes, where it is enriched in chromatoid bodies. MILI is essential for the self-renewing division and differentiation of germ line stem cells but does not affect initial establishment of the germ line stem cell population at 7 days postpartum. Furthermore, MILI forms a stable RNA-independent complex with eIF3a and associates with the eIF4E- and eIF4G-containing m(7)G cap-binding complex. In isolated 7 days postpartum seminiferous tubules containing mostly germ line stem cells, the mili mutation has no effect on the cellular mRNA level yet significantly reduces the rate of protein synthesis. These observations indicate that MILI may positively regulate translation and that such regulation is required for germ line stem cell self-renewal.