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

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 ∆E4 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 ∆VA-induced granules were PKR-dependent, ∆E4 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: ORLANDO SCUDERO

LAB HEAD: Benjamin A. Garcia

PROVIDER: PXD075408 | Pride | 2026-07-10

REPOSITORIES: Pride

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			Action	DRS
	221117_RL_Apex_10.raw	Raw
	221117_RL_Apex_11.raw	Raw
	221117_RL_Apex_14.raw	Raw
	221117_RL_Apex_15.raw	Raw
	221117_RL_Apex_16.raw	Raw

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