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Updated: Jul 17, 2025

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
The arginine methyltransferase PRMT5 promotes mucosal defense in the intestine
Juan E Hernandez1, Cristina Llorente2, Shengyun Ma1
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Abstract:
PRMT5 is a type II arginine methyltransferase abundantly expressed in the colonic epithelium. It is up-regulated in inflammatory bowel disease and colorectal cancer. However, its role in mucosal defense against enteric infection has not been studied. Here, we report that Prmt5 in the murine colon is up-regulated in response to Citrobacter rodentium infection. Pathogen clearance in mice with haploinsufficient expression of Prmt5 is significantly delayed compared with wildtype littermate controls. Transcriptomic analyses further reveal that PRMT5 regulates the expression of canonical crypt goblet cell genes involved in mucus production, assembly, and anti-microbial responses via methyltransferase activity-dependent and -independent mechanisms. Together, these findings uncover PRMT5 as a novel regulator of mucosal defense and a potential therapeutic target for treating intestinal diseases.
Insights
Protein arginine methyltransferase 5 (PRMT5) aids in colon mucosal defense against bacterial infection. Its deficiency impairs pathogen clearance, highlighting PRMT5 as a therapeutic target for intestinal diseases.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Protein arginine methyltransferase 5 (PRMT5) is highly expressed in the colon.
- PRMT5 is elevated in inflammatory bowel disease and colorectal cancer.
- The role of PRMT5 in mucosal defense against enteric pathogens remains uncharacterized.
Purpose of the Study:
- To investigate the role of PRMT5 in the colonic mucosal defense against enteric infection.
- To elucidate the mechanisms by which PRMT5 influences host defense.
Main Methods:
- Murine model of *Citrobacter rodentium* infection.
- Analysis of *Prmt5* expression in the colon.
- Assessment of pathogen clearance in wildtype and *Prmt5* haploinsufficient mice.
- Transcriptomic analysis to identify PRMT5-regulated genes.
Main Results:
- PRMT5 expression is induced in the murine colon during *Citrobacter rodentium* infection.
- Mice with reduced PRMT5 expression exhibit delayed pathogen clearance.
- PRMT5 regulates genes involved in mucus production, assembly, and antimicrobial responses.
- These regulatory functions involve both methyltransferase-dependent and -independent mechanisms.
Conclusions:
- PRMT5 is a novel regulator of colonic mucosal defense against enteric infection.
- PRMT5 plays a critical role in host defense by modulating goblet cell gene expression.
- PRMT5 represents a potential therapeutic target for intestinal diseases.
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