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. 2020 Aug 6;182(3):609-624.e21.
doi: 10.1016/j.cell.2020.06.022. Epub 2020 Jul 7.

RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis

Erika Sugisawa  1 , Yasunori Takayama  2 , Naoki Takemura  3 , Takeshi Kondo  4 , Shigetsugu Hatakeyama  4 , Yutaro Kumagai  5 , Masataka Sunagawa  2 , Makoto Tominaga  6 , Kenta Maruyama  7
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Free article

RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis

Erika Sugisawa et al. Cell. .
Free article

Abstract

Gastrointestinal enterochromaffin cells regulate bone and gut homeostasis via serotonin (5-hydroxytryptamine [5-HT]) production. A recent report suggested that gut microbes regulate 5-HT levels; however, the precise underlying molecular mechanisms are unexplored. Here, we reveal that the cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of Piezo1 increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders.

Keywords: 5-HT; Piezo1; bone formation; colitis; peristalsis; single-stranded RNA.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

Comment in

  • Microbial RNAs Pressure Piezo1 to Respond.
    Matute JD, Duan J, Blumberg RS. Matute JD, et al. Cell. 2020 Aug 6;182(3):542-544. doi: 10.1016/j.cell.2020.07.015. Cell. 2020. PMID: 32763186 Free PMC article.
  • RNA and the PIEZO force sensor.
    Beech DJ, Lichtenstein L. Beech DJ, et al. Cell Res. 2020 Oct;30(10):829-830. doi: 10.1038/s41422-020-00413-5. Cell Res. 2020. PMID: 32884138 Free PMC article. No abstract available.

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