TRIM14 expression is regulated by IRF-1 and IRF-2

Jingang Cui1, Xiao Xu1, Yutong Li1

  • 1Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.

FEBS Open Bio
|June 1, 2019
PubMed

Insights

Interferon (IFN)-I induces TRIM14 production via its promoter. Interferon regulatory factors (IRFs) 1 and 2 bind the TRIM14 promoter, with IRF-1 crucial for IFN-I-induced transcription and IRF-2 for basal transcription.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Tripartite motif-containing 14 (TRIM14) is a mitochondrial adaptor protein involved in innate immune signaling and antiviral defense.
  • TRIM14 expression is upregulated by Type I Interferon (IFN-I), but the regulatory mechanism remains unclear.

Purpose of the Study:

  • To elucidate the transcriptional regulation of TRIM14 by IFN-I.
  • To identify key promoter elements and transcription factors involved in TRIM14 gene expression.

Main Methods:

  • Promoter analysis to identify functional elements (GC box, ISRE).
  • Electrophoretic mobility shift assays (EMSAs) or similar to assess transcription factor binding.
  • Gene knockdown experiments (e.g., siRNA) to evaluate the role of IRF-1 and IRF-2.

Main Results:

  • A GC box and an Interferon-Stimulated Response Element (ISRE) are essential for basal TRIM14 transcription.
  • IFN-I activates the TRIM14 promoter through the ISRE.
  • Interferon regulatory factor-1 (IRF-1) and IRF-2 bind to the TRIM14 promoter, activating transcription.
  • IRF-1 knockdown significantly reduces IFN-α-induced TRIM14 transcription.
  • IRF-2 is critical for basal TRIM14 transcription but has a minimal role in IFN-α-induced transcription.

Conclusions:

  • IRF-1 is a key mediator of IFN-I-induced TRIM14 transcription.
  • IRF-2 plays a vital role in maintaining basal TRIM14 expression levels.
  • Understanding TRIM14 regulation by IRFs provides insights into innate immune responses.

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