Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond

Jiyoon Chung1, Yerim Lee1, Jimin Yoon1

  • 1Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

RNA Biology
|May 30, 2025
PubMed

Insights

Protein kinase R (PKR), an RNA-dependent kinase, has crucial roles beyond viral defense. It impacts gene expression, cell cycle, and differentiation in uninfected cells, with implications for disease.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Protein kinase R (PKR) is a key sensor of viral double-stranded RNA (dsRNA), initiating innate immune responses.
  • PKR activation involves dimerization on dsRNA and autophosphorylation, leading to downstream signaling.
  • Emerging evidence highlights PKR's roles in uninfected cells, interacting with cellular dsRNAs and regulators.

Purpose of the Study:

  • To review the diverse functions of PKR in physiological and pathological contexts outside of viral infection.
  • To explore PKR's involvement in cellular processes like gene expression, cell cycle, and differentiation.
  • To underscore the therapeutic potential of targeting PKR in various diseases.

Main Methods:

  • Literature review of existing research on PKR function.
  • Analysis of studies investigating PKR's interactions with cellular dsRNAs and protein regulators.
  • Synthesis of findings related to PKR's roles in both healthy and diseased states.

Main Results:

  • PKR misactivation in uninfected cells is linked to degenerative and inflammatory diseases.
  • In healthy cells, PKR influences mRNA splicing, translation, cell cycle, and differentiation.
  • PKR's functions extend beyond antiviral immunity, impacting cellular homeostasis.

Conclusions:

  • PKR is a versatile kinase with significant roles in cellular physiology and pathology independent of viral stimuli.
  • Understanding these non-canonical functions opens new avenues for cellular dsRNA research.
  • Targeting PKR presents promising therapeutic strategies for a range of diseases.

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