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Cell. 2019 Feb 21;176(5):1014-1025.e12. doi: 10.1016/j.cell.2019.01.037.

Regulation of MicroRNA Machinery and Development by Interspecies S-Nitrosylation.

Author information

1
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.
2
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.
3
Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
4
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
5
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; Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
6
Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA.
7
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; Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. Electronic address: jonathan.stamler@case.edu.

Abstract

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.

KEYWORDS:

C. elegans; S-nitrosylation; development; miRNA; microbiome; nitric oxide

PMID:
30794773
DOI:
10.1016/j.cell.2019.01.037

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