Yokohama National University, Yokohama, Kanagawa 240-8501, Japan.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3594-9. doi: 10.1073/pnas.0908664107. Epub 2010 Feb 2.
Nanos is one of the evolutionarily conserved proteins implicated in germ cell development. We have previously shown that NANOS2 plays an important role in both the maintenance and sexual development of germ cells. However, the molecular mechanisms underlying these events have remained elusive. In our present study, we found that NANOS2 localizes to the P-bodies, known centers of RNA degradation that are abundantly accumulated in male gonocytes. We further identified by immunoprecipitation that the components of the CCR4-NOT deadenylation complex are NANOS2-interacting proteins and found that NANOS2 promotes the localization of CNOT proteins to P-bodies in vivo. We also elucidated that the NANOS2/CCR4-NOT complex has deadenylase activity in vitro, and that some of the RNAs implicated in meiosis interact with NANOS2 and are accumulated in its absence. Our current data thus indicate that the expression of these RNA molecules is normally suppressed via a NANOS2-mediated mechanism. We propose from our current findings that NANOS2-interacting RNAs may be recruited to P-bodies and degraded by the enzymes contained therein through NANOS2-mediated deadenylation.
Nanos 蛋白是一种进化上保守的蛋白，与生殖细胞的发育有关。我们之前的研究表明 NANOS2 在生殖细胞的维持和性发育中发挥重要作用。然而，这些事件背后的分子机制仍不清楚。在我们目前的研究中，我们发现 NANOS2 定位于 P 体，这是一种已知的 RNA 降解中心，在雄性精原细胞中大量积累。我们进一步通过免疫沉淀鉴定出 CCR4-NOT 去腺苷酸化复合物的组成部分是 NANOS2 相互作用蛋白，并发现 NANOS2 促进 CNOT 蛋白在体内定位于 P 体。我们还阐明了 NANOS2/CCR4-NOT 复合物在体外具有脱腺苷酸酶活性，并且一些与减数分裂有关的 RNA 与 NANOS2 相互作用，并在其不存在时积累。因此，我们当前的数据表明，这些 RNA 分子的表达通常通过 NANOS2 介导的机制受到抑制。我们从当前的研究结果中提出，NANOS2 相互作用的 RNA 可能通过 NANOS2 介导的脱腺苷酸化被招募到 P 体并被其中的酶降解。
