Soper Sarah F C, van der Heijden Godfried W, Hardiman Tara C, Goodheart Mary, Martin Sandra L, de Boer Peter, Bortvin Alex
Biology Department, Johns Hopkins University, Baltimore, MD 21218, USA.
Dev Cell. 2008 Aug;15(2):285-97. doi: 10.1016/j.devcel.2008.05.015.
Tight control of transposon activity is essential for the integrity of the germline. Recently, a germ-cell-specific organelle, nuage, was proposed to play a role in transposon repression. To test this hypothesis, we disrupted a murine homolog of a Drosophila nuage protein Maelstrom. Effects on male meiotic chromosome synapsis and derepression of transposable elements (TEs) were observed. In the adult Mael(-/-) testes, LINE-1 (L1) derepression occurred at the onset of meiosis. As a result, Mael(-/-) spermatocytes were flooded with L1 ribonucleoproteins (RNPs) that accumulated in large cytoplasmic enclaves and nuclei. Mael(-/-) spermatocytes with nuclear L1 RNPs exhibited massive DNA damage and severe chromosome asynapsis even in the absence of SPO11-generated meiotic double-strand breaks. This study demonstrates that MAEL, a nuage component, is indispensable for the silencing of TEs and identifies the initiation of meiosis as an important step in TE control in the male germline.
严格控制转座子活性对于生殖系的完整性至关重要。最近,一种生殖细胞特异性细胞器——云(nuage),被认为在转座子抑制中发挥作用。为了验证这一假设,我们破坏了果蝇云蛋白Maelstrom的小鼠同源物。观察到其对雄性减数分裂染色体联会以及转座元件(TEs)去抑制的影响。在成年Mael(-/-)睾丸中,减数分裂开始时发生LINE-1(L1)去抑制。结果,Mael(-/-)精母细胞中充满了L1核糖核蛋白(RNPs),这些蛋白在大的细胞质区域和细胞核中积累。即使在没有SPO11产生的减数分裂双链断裂的情况下,含有核L1 RNPs的Mael(-/-)精母细胞也表现出大量DNA损伤和严重的染色体联会异常。这项研究表明,云成分MAEL对于TEs的沉默是不可或缺的,并确定减数分裂的开始是雄性生殖系中TE控制的一个重要步骤。