PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins

Greta Caprara1, Elena Prosperini2, Viviana Piccolo2

  • 1Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy; greta.caprara@ieo.it gioacchino.natoli@hunimed.eu.

Insights

Poly(ADP-ribose) polymerase 14 (PARP14) is induced by inflammation and aids nuclear accumulation of interferon-stimulated genes. PARP14 is crucial for antiviral responses and controlling bacterial infection in macrophages.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Poly(ADP-ribose) polymerase (PARP) superfamily enzymes regulate critical cellular processes.
  • Their precise roles in physiological and disease states remain incompletely understood.

Purpose of the Study:

  • To investigate the role of PARP14 in macrophage activation and antimicrobial responses.
  • To elucidate the molecular mechanisms underlying PARP14 function in inflammatory contexts.

Main Methods:

  • Murine macrophage activation with endotoxin.
  • Quantitative mass spectrometry to identify PARP14 interacting proteins.
  • Gene silencing (depletion) to assess functional requirements.
  • Analysis of antiviral gene transcription and bacterial proliferation.

Main Results:

  • PARP14 transcription is dynamically regulated during macrophage activation.
  • PARP14 is induced by inflammatory stimuli, translocates to the nucleus, and binds interferon-stimulated gene (ISG)-encoded proteins.
  • PARP14 is essential for the nuclear accumulation of specific ISG proteins.
  • PARP14 depletion impairs the transcription of primary antiviral genes (e.g., Ifnb1) and reduces IFN-β production.
  • PARP14 deficiency leads to increased Salmonella typhimurium proliferation in macrophages.

Conclusions:

  • PARP14 plays a significant role in regulating innate immune responses, particularly antiviral defense.
  • PARP14 facilitates nuclear functions of a subset of ISG-encoded proteins.
  • PARP14 is a key regulator in controlling microbial infections within macrophages.

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