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P300/RNA polymerase II mediates induction of the teleost viral RNA sensor MDA5 through the interferon regulatory

Wenxing Li1, Yuan Feng1, Yan Teng1

  • 1State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

The Journal of Biological Chemistry
|January 18, 2025
PubMed

Insights

Melanoma differentiation-associated gene 5 (MDA5) expression in fish is triggered by type I interferon (IFN) via JAK-STAT signaling. IFN regulatory factor 11 (IRF11) activates MDA5 transcription by recruiting key proteins to its promoter.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Melanoma differentiation-associated gene 5 (MDA5) detects cytosolic viral RNA and initiates type I interferon (IFN) production.
  • Mammalian MDA5 is IFN-inducible and regulated by IFN regulatory factor 1 (IRF1).
  • Regulation of teleost MDA5, despite its role in IFN production, remains largely unexplored.

Purpose of the Study:

  • To investigate the regulatory mechanism of MDA5 expression in the teleost, large yellow croaker (Larimichthys crocea).
  • To elucidate the role of IFN regulatory factor 11 (IRF11) in MDA5 transcription.

Main Methods:

  • Utilized the large yellow croaker (Lc) as a model organism.
  • Investigated the JAK-STAT signaling pathway in response to type I IFN (LcIFNi).
  • Analyzed the transcriptional regulation of LcMDA5 by LcIRF11, including promoter binding, protein recruitment (p300, Pol II), and histone modifications (H3K27ac, H3K4me3).

Main Results:

  • Type I IFN (LcIFNi) triggers LcMDA5 expression via JAK-STAT signaling and LcIRF11 phosphorylation.
  • LcIRF11 directly binds to the IFN-stimulated response element in the LcMDA5 promoter.
  • LcIRF11 recruits p300 and RNA polymerase II (Pol II), enhancing H3K27ac and H3K4me3 marks, thereby activating LcMDA5 transcription.

Conclusions:

  • IRF11 is a key regulator of MDA5 transcription in teleosts, binding the promoter and forming a transcriptional complex with p300 and Pol II.
  • This study reveals an ancient regulatory mechanism for MDA5 in lower vertebrates.
  • Findings provide insights into MDA5 function and evolution in innate immunity.
Keywords:
IRF11Larimichthys croceaMDA5histone modificationpromoter

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