Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos, 138648 Singapore.
Development. 2013 Sep;140(18):3819-25. doi: 10.1242/dev.099184. Epub 2013 Aug 7.
Mobilization of endogenous retrotransposons can destabilize the genome, an imminent danger during epigenetic reprogramming of cells in the germline. The P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway is known to silence retrotransposons in the mouse testes. Several piRNA pathway components localize to the unique, germline structure known as the nuage. In this study, we surveyed mouse ovaries and found, for the first time, transient appearance of nuage-like structures in oocytes of primordial follicles. Mouse vasa homolog (MVH), Piwi-like 2 (PIWIL2/MILI) and tudor domain-containing 9 (TDRD9) are present in these structures, whereas aggregates of germ cell protein with ankyrin repeats, sterile alpha motif and leucine zipper (GASZ) localize separately in the cytoplasm. Retrotransposons are silenced in primordial ovarian follicles, and de-repressed upon reduction of piRNA expression in Mvh, Mili or Gasz mutants. However, these null-mutant females, unlike their male counterparts, are fertile, uncoupling retrotransposon activation from sterility.
内源性逆转录转座子的激活会导致基因组不稳定,这在生殖细胞中进行表观遗传重编程时是一个迫在眉睫的危险。已知 P 元素诱导的软弱精巢(PIWI)相互作用 RNA(piRNA)途径可沉默小鼠睾丸中的逆转录转座子。几种 piRNA 途径成分定位于称为 nuage 的独特生殖细胞结构中。在这项研究中,我们调查了小鼠卵巢,首次发现原始卵泡中的卵母细胞中存在暂时性的 nuage 样结构。这些结构中存在小鼠 vas 同源物(MVH)、Piwi 样蛋白 2(PIWIL2/MILI)和 tudor 结构域包含蛋白 9(TDRD9),而含有锚蛋白重复序列、无活性α基序和亮氨酸拉链(GASZ)的生殖细胞蛋白聚集则分别定位于细胞质中。在原始卵泡中逆转录转座子被沉默,并且在 Mvh、Mili 或 Gasz 突变体中 piRNA 表达减少时被重新激活。然而,这些缺失突变体雌性与雄性不同,它们具有生育能力,将逆转录转座子的激活与不育分离。