2. Academic Validation
  3. Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants

Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants

  • bioRxiv. 2026 Feb 18:2026.02.17.706363. doi: 10.64898/2026.02.17.706363.
Robert T Steinbock 1 2,  Orlando B Scudero 1,  Joseph M Dybas 1 3,  Amber R N Abbott 1 2,  Katarzyna Kulej 1,  Richard Lauman 1,  Holly Chan 1,  Eva L Agostino 2,  Namrata Kumar 1,  Skyler Briggs 4,  Nicholas A Parenti 5,  Yize Li 5,  James M Burke 4,  Susan R Weiss 5,  Alexander M Price 6,  Matthew D Weitzman 1 5 7 8
Affiliations

Affiliations

  • 1 Division of Protective Immunity, and Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 2 Cell & Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.
  • 3 Center for Data-Driven Discovery in Biomedicine, Division of Neurosurgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 4 Department of Molecular Medicine, The Herbert Wertheim University of Florida Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, USA.
  • 5 Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 6 Genome Regulation and Cell Signaling, Ellen and Ronald Caplan Cancer Center, The Wistar Institute, Philadelphia, PA, USA.
  • 7 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 8 Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
PMID: 41756847 DOI: 10.64898/2026.02.17.706363
Abstract

Recognition of dsRNA triggers Antiviral defense mediated by PKR and OAS3/RNase L pathways through translational arrest and RNA decay. This is accompanied by assembly of distinct cytoplasmic ribonucleoprotein (RNP) condensates termed stress granules (SGs) and RNase L-dependent bodies (RLBs). Here we show that adenovirus Infection differentially modulates dsRNA sensors and RNP granule assembly. Infection with splicing-defective ΔE4 mutant leads to dsRNA accumulation and activation of both PKR and OAS3/RNase L, promoting formation of RLB-like granules. In contrast, mutants lacking virus-associated (VA) RNAs trigger PKR activation and assembly of SGs despite absence of detectable dsRNA. Proteomic analysis revealed distinct protein compositions of canonical SGs and RLBs, which were reflected in virus-induced granules. While ΔVA-induced granules were PKR-dependent, ΔE4 mutants induced RLB-like granules independently of PKR and RNase L. In these cells, granule assembly coincided with translational arrest independent of eIF2α phosphorylation, indicating additional pathways linking nuclear dsRNA sensing to translational control and RNP granule assembly during viral Infection. These findings provide novel insights into how distinct dsRNA sensors modulate translation and RNP condensates in response to stress.

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