Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, The USTC RNA Institute, Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Life Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, Anhui, 230027, China.
National Institute of Biological Sciences, Beijing, 102206, China.
Nat Commun. 2024 Jul 10;15(1):5799. doi: 10.1038/s41467-024-50027-3.
Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify an uncharted subcompartment of the C. elegans germ granule, which we term the E granule. The E granule is nonrandomly positioned within the germ granule. We identify five proteins that localize to the E granule, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5' regions of a subset of germline-expressed mRNAs. Defects in E granule assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a distinct subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.
生殖质是存在于大多数动物生殖细胞中的生物分子凝聚物。生殖质的一个功能是通过组织 mRNA 调节机制，包括基于小 RNA 的基因调节途径，帮助维持生殖细胞的全能性。线虫的生殖质被分隔成多个亚区，其生物学功能在很大程度上是未知的。在这里，我们鉴定了线虫生殖质的一个未被描述的亚区，我们将其命名为 E 颗粒。E 颗粒在生殖质中是非随机定位的。我们鉴定了五个定位于 E 颗粒的蛋白质，包括 RNA 依赖性 RNA 聚合酶 (RdRP) EGO-1、与 Dicer 相关的解旋酶 DRH-3、含 Tudor 结构域的蛋白 EKL-1，以及两个内在无序的蛋白质 EGC-1 和 ELLI-1。EGO-1 定位于 E 颗粒中，能够合成一类特殊的 22G RNA，这些 RNA 仅来源于一小部分生殖系表达的 mRNA 的 5' 区域。E 颗粒组装缺陷会引起内源性 siRNA 的无序产生，从而扰乱生殖力和 RNAi 反应。我们的结果定义了线虫生殖质的一个独特的亚区，并表明生殖质区室化的一个功能是促进特殊种类的小调控 RNA 的局部产生。
