Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
1] Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan [2].
Nature. 2014 May 29;509(7502):633-6. doi: 10.1038/nature13315. Epub 2014 May 14.
The silkworm Bombyx mori uses a WZ sex determination system that is analogous to the one found in birds and some reptiles. In this system, males have two Z sex chromosomes, whereas females have Z and W sex chromosomes. The silkworm W chromosome has a dominant role in female determination, suggesting the existence of a dominant feminizing gene in this chromosome. However, the W chromosome is almost fully occupied by transposable element sequences, and no functional protein-coding gene has been identified so far. Female-enriched PIWI-interacting RNAs (piRNAs) are the only known transcripts that are produced from the sex-determining region of the W chromosome, but the function(s) of these piRNAs are unknown. Here we show that a W-chromosome-derived, female-specific piRNA is the feminizing factor of B. mori. This piRNA is produced from a piRNA precursor which we named Fem. Fem sequences were arranged in tandem in the sex-determining region of the W chromosome. Inhibition of Fem-derived piRNA-mediated signalling in female embryos led to the production of the male-specific splice variants of B. mori doublesex (Bmdsx), a gene which acts at the downstream end of the sex differentiation cascade. A target gene of Fem-derived piRNA was identified on the Z chromosome of B. mori. This gene, which we named Masc, encoded a CCCH-type zinc finger protein. We show that the silencing of Masc messenger RNA by Fem piRNA is required for the production of female-specific isoforms of Bmdsx in female embryos, and that Masc protein controls both dosage compensation and masculinization in male embryos. Our study characterizes a single small RNA that is responsible for primary sex determination in the WZ sex determination system.
家蚕采用 WZ 性别决定系统，类似于鸟类和某些爬行动物的性别决定系统。在这个系统中，雄性有两条 Z 性染色体，而雌性有 Z 和 W 性染色体。家蚕的 W 染色体在雌性决定中起主导作用，这表明在这条染色体上存在一个显性雌性化基因。然而，W 染色体几乎完全被转座元件序列占据，到目前为止还没有鉴定出功能性的蛋白质编码基因。雌性富集的 PIWI 相互作用 RNA（piRNA）是唯一已知从 W 染色体性别决定区产生的转录本，但这些 piRNA 的功能尚不清楚。在这里，我们表明，一条 W 染色体衍生的、雌性特异性的 piRNA 是家蚕的雌性化因子。这条 piRNA 是由我们命名为 Fem 的 piRNA 前体产生的。Fem 序列在 W 染色体的性别决定区串联排列。在雌性胚胎中抑制 Fem 衍生的 piRNA 介导的信号转导导致了 B. mori 双性（Bmdsx）的雄性特异性剪接变体的产生，Bmdsx 基因在性别分化级联的下游起作用。在 B. mori 的 Z 染色体上鉴定到 Fem 衍生的 piRNA 的靶基因。这个基因，我们命名为 Masc，编码一个 CCCH 型锌指蛋白。我们表明，Fem piRNA 对 Masc 信使 RNA 的沉默是雌性胚胎中 Bmdsx 雌性特异性同工型产生所必需的，并且 Masc 蛋白控制雄性胚胎中的剂量补偿和雄性化。我们的研究描述了一个单一的小 RNA，它负责 WZ 性别决定系统中的初级性别决定。
