@article{c6f743590a834fef91162a15313ef25c,
title = "Regulation of MicroRNA Machinery and Development by Interspecies S-Nitrosylation",
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. Microbiome-derived nitric oxide causes widespread post-translational modification of host proteins to regulate host functions and physiology.",
keywords = "C. elegans, S-nitrosylation, development, miRNA, microbiome, nitric oxide",
author = "Puneet Seth and Hsieh, {Paishiun N.} and Suhib Jamal and Liwen Wang and Gygi, {Steven P.} and Jain, {Mukesh K.} and Jeff Coller and Stamler, {Jonathan S.}",
note = "Funding Information: We thank Marian Kalocsay for help with proteomic analyses, Precious J. McLaughlin for technical assistance, Divya Seth for valuable input, and Thomas J. Sweet for help with RNA protocols. The AIN-1 antibody was a kind gift from John K. Kim at Johns Hopkins University. This work was supported by NIH grants R01 GM099921, R01 DK119506, P01 HL075443, and P01 HL128192 to J.S.S., T32 GM007250 and F30 AG054237 to P.N.H., and R35 HL135789 to M.K.J. Funding Information: We thank Marian Kalocsay for help with proteomic analyses, Precious J. McLaughlin for technical assistance, Divya Seth for valuable input, and Thomas J. Sweet for help with RNA protocols. The AIN-1 antibody was a kind gift from John K. Kim at Johns Hopkins University. This work was supported by NIH grants R01 GM099921, R01 DK119506, P01 HL075443, and P01 HL128192 to J.S.S., T32 GM007250 and F30 AG054237 to P.N.H., and R35 HL135789 to M.K.J., P.S., P.N.H., and S.J. performed the experiments. L.W. and S.P.G. performed mass-spec analysis. P.S., P.N.H., J.C., and J.S.S. designed the research. P.S., P.N.H., J.C., M.J., and J.S.S. interpreted the data. J.S.S., J.C., and M.K.J. supervised the research. P.S., P.N.H., J.C., and J.S.S. wrote the manuscript incorporating comments from all the authors., The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = feb,
day = "21",
doi = "10.1016/j.cell.2019.01.037",
language = "English (US)",
volume = "176",
pages = "1014--1025.e12",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}