NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression of specific RNAs
NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression of specific RNAs
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DOI：
10.1073/pnas.0908664107
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发表时间：
2010-02-23
影响因子：
11.1
通讯作者：
Saga, Yumiko
中科院分区：
文献类型：
--
作者：
Suzuki, Atsushi;Igarashi, Katsuhide;Saga, Yumiko
Nanos是一种进化保守的蛋白质，与生殖细胞发育有关。我们之前已经证明，NANOS2在生殖细胞的维持和性发育中都扮演着重要的角色。然而，这些事件背后的分子机制仍然难以捉摸。在我们目前的研究中，我们发现NANOS2定位于P小体，这是已知的RNA降解中心，在男性性腺细胞中大量积累。我们进一步通过免疫沉淀鉴定了CCR4-NOT去烯化复合体的组成成分是与NANOS2相互作用的蛋白质，并发现NANOS2促进了CNOT蛋白在体内的P小体定位。我们还阐明了NANOS2/CCR4-NOT复合体在体外具有死烯基酶活性，并且一些参与减数分裂的RNA与NANOS2相互作用并在没有NANOS2的情况下积累。因此，我们目前的数据表明，这些RNA分子的表达通常是通过NANOS2介导的机制抑制的。根据我们目前的发现，我们认为与NANOS2相互作用的RNA可能被招募到P-小体中，并通过NANOS2介导的去烯化作用被其中包含的酶降解。
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.