Related Experiment Video

Updated: Jul 19, 2025

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
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XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells

Tao Zou1,2, Meng Zhou1,2, Akansha Gupta1,2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

Biorxiv : the Preprint Server for Biology
|August 14, 2023
PubMed

Insights

Deleting XRN1 activates protein kinase R (PKR) in cancer cells, leading to cell death. This suggests XRN1 as a potential therapeutic target for cancers with high interferon-stimulated gene expression.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Inducing viral mimicry by activating double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy.
  • Targeting molecular regulators of dsRNA sensing pathways can induce viral mimicry.

Approach:

  • Investigated the role of exoribonuclease XRN1 in regulating the dsRNA sensor protein kinase R (PKR).
  • Examined the impact of XRN1 deletion on cancer cell viability and PKR activation in cells with high interferon-stimulated gene (ISG) expression.

Key Points:

  • XRN1 acts as a negative regulator of PKR in cancer cells with high ISG expression.
  • XRN1 deletion leads to PKR activation and cancer cell lethality.
  • Interferon signaling modulation (e.g., ruxolitinib, interferon-β) affects PKR levels and sensitivity to XRN1 deletion.
  • XRN1 deletion results in the accumulation of endogenous complementary sense/anti-sense RNAs, potential PKR ligands.

Conclusions:

  • XRN1 regulates PKR activity, particularly in cancer cells with an activated interferon state.
  • XRN1 is a potential therapeutic target for specific cancer types.
Keywords:
PKRRNA sensingXRN1cancerinterferon

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