Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Chromosome Res. 2013 Dec;21(6-7):573-86. doi: 10.1007/s10577-013-9383-7.
While initial studies of small RNA-mediated gene regulatory pathways focused on the cytoplasmic functions of such pathways, identifying roles for Argonaute/small RNA pathways in modulating chromatin and organizing the genome has become a topic of intense research in recent years. Nuclear regulatory mechanisms for Argonaute/small RNA pathways appear to be widespread, in organisms ranging from plants to fission yeast, Caenorhabditis elegans to humans. As the effectors of small RNA-mediated gene regulatory pathways, Argonaute proteins guide the chromatin-directed activities of these pathways. Of particular interest is the C. elegans Argonaute, chromosome segregation and RNAi deficient (CSR-1), which has been implicated in such diverse functions as organizing the holocentromeres of worm chromosomes, modulating germline chromatin, protecting the genome from foreign nucleic acid, regulating histone levels, executing RNAi, and inhibiting translation in conjunction with Pumilio proteins. CSR-1 interacts with small RNAs known as 22G-RNAs, which have complementarity to 25 % of the protein coding genes. This peculiar Argonaute is the only essential C. elegans Argonaute out of 24 family members in total. Here, we summarize the current understanding of CSR-1 functions in the worm, with emphasis on the chromatin-directed activities of this ever-intriguing Argonaute.
虽然最初的小 RNA 介导的基因调控途径的研究集中在这些途径的细胞质功能上，但近年来，鉴定 Argonaute/small RNA 途径在调节染色质和组织基因组方面的作用已成为一个研究热点。Argonaute/small RNA 途径的核调控机制似乎很广泛，存在于从植物到裂殖酵母、秀丽隐杆线虫到人类等生物体中。作为小 RNA 介导的基因调控途径的效应物，Argonaute 蛋白指导这些途径的染色质导向活性。特别有趣的是线虫 Argonaute、染色体分离和 RNAi 缺陷（CSR-1），它与组织线虫染色体的全着丝粒、调节生殖细胞染色质、保护基因组免受外来核酸的侵害、调节组蛋白水平、执行 RNAi 以及与 Pumilio 蛋白结合抑制翻译等多种功能有关。CSR-1 与被称为 22G-RNAs 的小 RNA 相互作用，这些小 RNA 与 25%的蛋白质编码基因具有互补性。这种特殊的 Argonaute 是线虫中唯一必需的 Argonaute，共有 24 个家族成员。在这里，我们总结了 CSR-1 在蠕虫中的功能的现有认识，重点介绍了这种令人着迷的 Argonaute 的染色质导向活性。
