Reevaluation of Piezo1 as a gut RNA sensor
- National Institutes of Health, United States
- Howard Hughes Medical Institute, Scripps Research Institute, United States
Abstract
Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent findings point to a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observe that fecal extracts and ssRNA can stimulate calcium influx in certain cell lines, this response is independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA show similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data have been deposited on the GEO website.
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Reevaluation of Piezo1 as a gut RNA sensorNCBI Gene Expression Omnibus, GSE213903.
Article and author information
Author details
Alexander Theodore Chesler
Funding
National Center for Complementary and Integrative Health (Intramural funds)
- Alexander Theodore Chesler
National Institute of Neurological Disorders and Stroke (Intramural funds)
- Alexander Theodore Chesler
National Center for Advancing Translational Sciences (Intramural funds)
- Alexander Theodore Chesler
Howard Hughes Medical Institute
- Ardem Patapoutian
National Institutes of Health (R35 NS105067)
- Ardem Patapoutian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#1365) of the NINDS-IRP.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Reevaluation of Piezo1 as a gut RNA sensor
eLife 11:e83346.
https://doi.org/10.7554/eLife.83346
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