Institute of Molecular Biology, Mainz, Germany.
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
Curr Top Dev Biol. 2021;144:45-89. doi: 10.1016/bs.ctdb.2020.08.002. Epub 2020 Oct 3.
A diversity of gene regulatory mechanisms drives the changes in gene expression required for animal development. Here, we discuss the developmental roles of a class of gene regulatory factors composed of a core protein subunit of the Argonaute family and a 21-26-nucleotide RNA cofactor. These represent ancient regulatory complexes, originally evolved to repress genomic parasites such as transposons, viruses and retroviruses. However, over the course of evolution, small RNA-guided pathways have expanded and diversified, and they play multiple roles across all eukaryotes. Pertinent to this review, Argonaute and small RNA-mediated regulation has acquired numerous functions that affect all aspects of animal life. The regulatory function is provided by the Argonaute protein and its interactors, while the small RNA provides target specificity, guiding the Argonaute to a complementary RNA. C. elegans has 19 different, functional Argonautes, defining distinct yet interconnected pathways. Each Argonaute binds a relatively well-defined class of small RNA with distinct molecular properties. A broad classification of animal small RNA pathways distinguishes between two groups: (i) the microRNA pathway is involved in repressing relatively specific endogenous genes and (ii) the other small RNA pathways, which effectively act as a genomic immune system to primarily repress expression of foreign or "non-self" RNA while maintaining correct endogenous gene expression. microRNAs play prominent direct roles in all developmental stages, adult physiology and lifespan. The other small RNA pathways act primarily in the germline, but their impact extends far beyond, into embryogenesis and adult physiology, and even to subsequent generations. Here, we review the mechanisms and developmental functions of the diverse small RNA pathways of C. elegans.
多种基因调控机制驱动了动物发育所需的基因表达变化。在这里，我们讨论了一类由 Argonaute 家族核心蛋白亚基和 21-26 个核苷酸 RNA 辅助因子组成的基因调控因子的发育作用。这些代表了古老的调控复合物，最初是为了抑制转座子、病毒和逆转录病毒等基因组寄生虫而进化的。然而，在进化过程中，小 RNA 引导途径不断扩展和多样化，它们在所有真核生物中发挥着多种作用。与本综述相关的是，Argonaute 和小 RNA 介导的调控已经获得了许多影响动物生命各个方面的功能。调控功能由 Argonaute 蛋白及其相互作用蛋白提供，而小 RNA 则提供靶标特异性，将 Argonaute 引导至互补的 RNA。秀丽隐杆线虫有 19 种不同的、功能齐全的 Argonautes，定义了不同但相互关联的途径。每个 Argonaute 都结合了相对明确的一类具有不同分子特性的小 RNA。动物小 RNA 途径的广泛分类区分了两组：（i）microRNA 途径参与抑制相对特定的内源性基因；（ii）其他小 RNA 途径，它们有效地作为基因组免疫系统，主要抑制外来或“非自身”RNA 的表达，同时维持正确的内源性基因表达。microRNAs 在所有发育阶段、成年生理和寿命中都发挥着突出的直接作用。其他小 RNA 途径主要在生殖系中起作用，但它们的影响远远超出生殖系，延伸到胚胎发生和成年生理，甚至延伸到后代。在这里，我们综述了秀丽隐杆线虫不同小 RNA 途径的机制和发育功能。
