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LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages

Tina Ruggiero1, Michele Trabucchi, Francesca De Santa

  • 1RNA Technology Laboratory, Centro Biotecnologie Avanzate, Genoa, Italy.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 9, 2009
PubMed

Insights

MicroRNAs (miRNAs) regulate immune responses. Lipopolysaccharide (LPS) induces miR-155 maturation via KSRP, which then fine-tunes inflammation mediator expression in macrophages.

Area of Science:

  • Immunology
  • Molecular Biology
  • Post-transcriptional Regulation

Background:

  • Immune system homeostasis and response to pathogens rely on post-transcriptional regulation.
  • MicroRNAs (miRNAs) are key regulators of gene expression, particularly in immune cells like macrophages.

Purpose of the Study:

  • To investigate the role of miRNAs in macrophage activation induced by lipopolysaccharide (LPS).
  • To elucidate the specific mechanisms of microRNA regulation during inflammatory responses.

Main Methods:

  • Utilized Dicer knockout in bone marrow-derived macrophages (BMDMs) to assess miRNA function.
  • Performed miRNA microarray analysis to identify LPS-responsive miRNAs.
  • Investigated the role of KH-type splicing regulatory protein (KSRP) in miR-155 biogenesis.

Main Results:

  • Dicer knockout enhanced LPS-induced expression of certain inflammation mediators.
  • LPS significantly induced miR-155 expression in BMDMs, dependent on enhanced precursor maturation.
  • KSRP was identified as a key factor promoting miR-155 precursor maturation, thereby regulating inflammation.

Conclusions:

  • LPS triggers a post-transcriptional regulatory pathway for miR-155 biogenesis involving KSRP.
  • Induced miR-155 plays a crucial role in fine-tuning the expression of inflammation mediators during LPS stimulation.
  • This pathway highlights a novel mechanism for controlling immune responses at the post-transcriptional level.

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