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.

Life Science Alliance
|September 4, 2023
PubMed

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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