Department of Biology, Colorado State University, Fort Collins, CO 80523, USA; Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA.
Department of Biology, Colorado State University, Fort Collins, CO 80523, USA.
Cell Rep. 2019 Dec 3;29(10):3187-3199.e4. doi: 10.1016/j.celrep.2019.10.114.
The germline contains an immortal cell lineage that ensures the faithful transmission of genetic and, in some instances, epigenetic information from one generation to the next. Here, we show that in Caenorhabditis elegans, the small RNA 3'-2'-O-methyltransferase henn-1/HEN1 is required for sustained fertility across generations. In the absence of henn-1, animals become progressively less fertile, becoming sterile after ∼30 generations at 25°C. Sterility in henn-1 mutants is accompanied by severe defects in germline proliferation and maintenance. The requirement for henn-1 in transgenerational fertility is likely due to its role in methylating and, thereby, stabilizing Piwi-interacting RNAs (piRNAs). However, despite being essential for piRNA stability in embryos, henn-1 is not required for piRNA stability in adults. Thus, we propose that methylation is important for the role of piRNAs in establishing proper gene silencing during early stages of development but is dispensable for their role in the proliferated germline.
生殖细胞系包含一个永生细胞系，它确保了遗传信息，在某些情况下还有表观遗传信息从一代传递到下一代的忠实传递。在这里，我们表明在秀丽隐杆线虫中，小 RNA 3'-2'-O-甲基转移酶 henn-1/HEN1 是跨代维持生育力所必需的。在没有 henn-1 的情况下，动物的生育能力逐渐下降，在 25°C 下大约 30 代后就会变得不育。henn-1 突变体的不育伴随着生殖系增殖和维持的严重缺陷。henn-1 在跨代生育力中的需求可能是由于它在甲基化和稳定 Piwi 相互作用 RNA（piRNA）方面的作用。然而，尽管 henn-1 对胚胎中 piRNA 的稳定性至关重要，但它在成年期 piRNA 的稳定性中并非必需。因此，我们提出甲基化对于 piRNA 在发育早期建立适当的基因沉默作用很重要，但对于它们在增殖的生殖系中的作用是可有可无的。
