Institute for Transformative Molecular Medicine and Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, 2103 Cornell Road, Cleveland, OH 44106, USA; Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Cell. 2019 Feb 21;176(5):1014-1025.e12. doi: 10.1016/j.cell.2019.01.037.
Bioactive molecules can pass between microbiota and host to influence host cellular functions. However, general principles of interspecies communication have not been discovered. We show here in C. elegans that nitric oxide derived from resident bacteria promotes widespread S-nitrosylation of the host proteome. We further show that microbiota-dependent S-nitrosylation of C. elegans Argonaute protein (ALG-1)-at a site conserved and S-nitrosylated in mammalian Argonaute 2 (AGO2)-alters its function in controlling gene expression via microRNAs. By selectively eliminating nitric oxide generation by the microbiota or S-nitrosylation in ALG-1, we reveal unforeseen effects on host development. Thus, the microbiota can shape the post-translational landscape of the host proteome to regulate microRNA activity, gene expression, and host development. Our findings suggest a general mechanism by which the microbiota may control host cellular functions, as well as a new role for gasotransmitters.
生物活性分子可以在微生物群落和宿主之间传递，从而影响宿主细胞功能。然而，种间通讯的一般原则尚未被发现。我们在这里在秀丽隐杆线虫中表明，来自常驻细菌的一氧化氮促进宿主蛋白质组的广泛 S-亚硝化。我们进一步表明，秀丽隐杆线虫 Argonaute 蛋白 (ALG-1) 的微生物群依赖性 S-亚硝化-在哺乳动物 Argonaute 2 (AGO2) 中保守且 S-亚硝化的位点-改变了其通过 microRNAs 控制基因表达的功能。通过选择性地消除微生物群落中一氧化氮的产生或 ALG-1 中的 S-亚硝化，我们揭示了对宿主发育的意外影响。因此，微生物群可以塑造宿主蛋白质组的翻译后景观，以调节 microRNA 活性、基因表达和宿主发育。我们的发现表明了微生物群可能控制宿主细胞功能的一般机制，以及气体递质的新作用。
