Morita Shumpei, Ota Ryoma, Hayashi Makoto, Kobayashi Satoru
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan; Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
iScience. 2020 Mar 27;23(3):100950. doi: 10.1016/j.isci.2020.100950. Epub 2020 Feb 28.
Cell-cycle quiescence is a common feature of early germline development in many animal species. In Drosophila germline progenitors (pole cells), both G2/M and G1/S transitions are blocked. G2/M transition is repressed by maternal Nanos through suppression of Cyclin B production. However, the molecular mechanism underlying blockage of G1/S transition remains elusive. We found that repression of miR-10404 expression is required to block G1/S transition in pole cells. Expression of miR-10404, a microRNA encoded within the internal transcribed spacer 1 of rDNA, is repressed in early pole cells by maternal polar granule component. This repression delays the degradation of maternal dacapo mRNA, which encodes an inhibitor of G1/S transition. Moreover, derepression of G1/S transition in pole cells causes defects in their maintenance and their migration into the gonads. Our observations reveal the mechanism inhibiting G1/S transition in pole cells and its requirement for proper germline development.
细胞周期静止是许多动物物种早期生殖系发育的一个共同特征。在果蝇生殖系祖细胞(极细胞)中,G2/M期和G1/S期转换均被阻断。母源Nanos通过抑制周期蛋白B的产生来抑制G2/M期转换。然而,G1/S期转换受阻的分子机制仍不清楚。我们发现,抑制miR-10404的表达是阻断极细胞中G1/S期转换所必需的。miR-10404是一种由核糖体DNA内转录间隔区1编码的微小RNA,其表达在早期极细胞中被母源极颗粒成分所抑制。这种抑制作用延迟了母源dacapo mRNA的降解,dacapo mRNA编码一种G1/S期转换的抑制剂。此外,极细胞中G1/S期转换的去抑制会导致其维持以及向性腺迁移方面的缺陷。我们的观察结果揭示了极细胞中抑制G1/S期转换的机制及其对生殖系正常发育的必要性。