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Updated: Mar 28, 2026

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
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.
Abstract:
Protein kinase R (PKR) is a serine/threonine kinase that recognizes double-stranded RNAs (dsRNAs) to initiate innate immune signalling during viral infection. PKR dimerizes on long dsRNAs and undergoes autophosphorylation. Phosphorylated/Activated PKR then catalyses the phosphorylation of numerous substrates to control global translation, inflammatory response, and cell signalling pathways. While primarily known for its antiviral role, emerging evidence suggests that PKR can play multifaceted roles in uninfected cells by interacting with cellular dsRNAs and protein regulators. The misactivation of PKR in uninfected cells is associated with many degenerative and inflammatory diseases. Even in healthy cells, PKR can affect gene expression by controlling mRNA splicing and gene-specific translation under stress. In addition, PKR can modulate cell cycle progression and promote cellular differentiation in several tissue types. This review explores PKR function in various pathological and physiological contexts in the absence of viral stimuli. By elucidating these diverse functions, we aim to highlight the perspectives in cellular dsRNA research and the therapeutic implications of targeting PKR, stimulating further research into this versatile and essential RNA-dependent kinase.
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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