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Updated: Apr 28, 2026
Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator
Yoosik Kim1, Jung Hyun Lee1, Jong-Eun Park1
1Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Abstract:
dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well known for its roles in immune response. Upon binding to viral dsRNA, PKR undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates translation and multiple signaling pathways in infected cells. Here, we found that PKR is activated in uninfected cells, specifically during mitosis, by binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu-containing RNAs are segregated in the cytosol and nucleus of interphase cells, respectively, they interact during mitosis when nuclear structure is disrupted. Once phosphorylated, PKR suppresses global translation by phosphorylating the α subunit of eukaryotic initiation factor 2 (eIF2α). In addition, pPKR acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels of multiple mitotic factors such as cyclins A and B and Polo-like kinase 1 and phosphorylation of histone H3. Disruption of PKR activation via RNAi or expression of a transdominant-negative mutant leads to misregulation of the mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our study unveils a novel function of PKR and endogenous dsRNAs as signaling molecules during the mitosis of uninfected cells.
Insights
Protein kinase R (PKR) activates during mitosis in uninfected cells by binding to endogenous dsRNAs. This regulates translation and mitotic factors, revealing a new signaling role for PKR in cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Protein kinase R (PKR) is a key enzyme in the immune response, activated by viral double-stranded RNA (dsRNA) to regulate translation.
- PKR's role in uninfected cells, particularly during mitosis, has not been well understood.
Purpose of the Study:
- To investigate the novel function of PKR in uninfected cells during mitosis.
- To identify the interaction partners and regulatory mechanisms of PKR during cell division.
Main Methods:
- Utilized RNA interference (RNAi) and dominant-negative mutants to disrupt PKR activation.
- Analyzed the effects of PKR disruption on mitotic factors, translation, and cell cycle progression.
- Investigated the interaction between PKR and dsRNAs during different cell cycle phases.
Main Results:
- PKR is activated during mitosis in uninfected cells through binding to dsRNAs from inverted Alu repeats (IRAlus).
- Activated PKR phosphorylates eIF2α, suppressing global translation, and acts as an upstream kinase for c-Jun N-terminal kinase.
- PKR regulates key mitotic factors including cyclins A and B, Polo-like kinase 1, and histone H3 phosphorylation.
- Disruption of PKR activation leads to mitotic defects, including delayed progression and cytokinesis failure.
Conclusions:
- PKR has a novel role in regulating mitosis in uninfected cells.
- Endogenous dsRNAs, specifically IRAlus, act as signaling molecules to activate PKR during cell division.
- PKR-mediated signaling is crucial for accurate mitotic progression and cytokinesis.
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