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The Splicing Factor hnRNP M Is a Critical Regulator of Innate Immune Gene Expression in Macrophages

Kelsi O West1, Haley M Scott1, Sylvia Torres-Odio1

  • 1Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807, USA.

Cell Reports
|November 7, 2019
PubMed

Insights

The splicing factor hnRNP M represses innate immune genes. Pathogen sensing regulates hnRNP M, controlling gene expression and macrophage activation crucial for immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • Transcriptional control of innate immunity is understood, but the role of pre-mRNA splicing in macrophage activation remains unclear.
  • Splicing factors are essential for gene expression, but their specific roles in innate immune responses are largely uncharacterized.

Purpose of the Study:

  • To investigate the role of pre-mRNA splicing, specifically the splicing factor hnRNP M, in regulating innate immune gene expression during macrophage activation.
  • To determine how pathogen sensing pathways influence the function of splicing factors like hnRNP M.

Main Methods:

  • Utilized genetic manipulation to study the function of hnRNP M in macrophages.
  • Investigated the impact of hnRNP M loss and specific mutations on gene expression following innate immune stimuli.
  • Analyzed the role of pathogen sensing cascades in regulating splicing factor phosphorylation.

Main Results:

  • hnRNP M acts as a critical repressor of innate immune gene expression.
  • Loss of hnRNP M leads to hyperinduction of inflammatory and antimicrobial genes upon innate immune stimulation.
  • Pathogen sensing pathways regulate hnRNP M phosphorylation, impacting its ability to control innate immune gene induction.

Conclusions:

  • Pre-mRNA splicing is a critical regulatory mechanism in innate immunity, influenced by pathogen sensing.
  • Splicing factor phosphorylation, regulated by pattern recognition receptor signaling, plays a key role in innate immune outcomes.
  • hnRNP M is a novel regulator of innate immune gene expression, linking splicing to macrophage activation.
Keywords:
RNA binding proteinSalmonellahnRNPinflammationinnate immune responsemacrophagephosphorylationpre-mRNA splicingspliceosometoll-like receptor

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