Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells.
Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells.
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DOI：
10.1242/bio.20149308
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发表时间：
2014-11-21
期刊：
影响因子：
2.4
通讯作者：
Saga Y
中科院分区：
文献类型：
--
作者：
Suzuki A;Niimi Y;Saga Y
NANOS2 和 NANOS3 属于 Nanos 蛋白家族，含有保守的锌指结构域，由两个连续的 CCHC 型锌指基序组成，有助于小鼠生殖细胞的发育。先前的研究表明这两种蛋白质存在冗余且不同的功能。 NANOS2 挽救了 NANOS3 在维持原始生殖细胞方面的功能，而 NANOS3 未能取代 NANOS2 在雄性生殖细胞途径中的功能。然而，Nanos3 条件等位基因的缺乏阻碍了 NANOS2 和 NANOS3 对雄性生殖细胞途径的各自贡献的描述。此外，这些蛋白质独特功能的分子机制仍未被探索。在这里，我们报告了对表达 NANOS2 变体的转基因小鼠系的意外观察，该变体在锌指结构域中含有突变。 Nanos2 和 Nanos3 的转录在该转基因的存在下受到严重损害，导致雄性性腺中模仿 Nanos2/Nanos3 双无效条件。在这些转基因小鼠中，参与RNA代谢的P体消失，生殖细胞分化比Nanos2缺失小鼠受到更严重的影响，表明NANOS3部分替代了NANOS2的功能。此外，与 NANOS2 类似，我们发现 NANOS3 与 CCR4-NOT 去腺苷化复合物相关，但通过与 CNOT8 直接相互作用，这与 NANOS2 中的 CNOT1 不同。这种交替的相互作用可能解释了 NANOS2 和 NANOS3 功能冗余和差异的分子基础。
NANOS2 and NANOS3 belong to the Nanos family of proteins that contain a conserved zinc finger domain, which consists of two consecutive CCHC-type zinc finger motifs, and contribute to germ cell development in mice. Previous studies indicate that there are redundant and distinct functions of these two proteins. NANOS2 rescues NANOS3 functions in the maintenance of primordial germ cells, whereas NANOS3 fails to replace NANOS2 functions in the male germ cell pathway. However, the lack of a conditional allele of Nanos3 has hampered delineation of each contribution of NANOS2 and NANOS3 to the male germ cell pathway. In addition, the molecular mechanism underlying the distinct functions of these proteins remains unexplored. Here, we report an unexpected observation of a transgenic mouse line expressing a NANOS2 variant harboring mutations in the zinc finger domain. Transcription of Nanos2 and Nanos3 was strongly compromised in the presence of this transgene, which resulted in the mimicking of the Nanos2/Nanos3 double-null condition in the male gonad. In these transgenic mice, P-bodies involved in RNA metabolism had disappeared and germ cell differentiation was more severely affected than that in Nanos2-null mice, indicating that NANOS3 partially substitutes for NANOS2 functions. In addition, similar to NANOS2, we found that NANOS3 associated with the CCR4-NOT deadenylation complex but via a direct interaction with CNOT8, unlike CNOT1 in the case of NANOS2. This alternate interaction might account for the molecular basis of the functional redundancy and differences in NANOS2 and NANOS3 functions.
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