Adenovirus prevents dsRNA formation by promoting efficient splicing of viral RNA

Alexander M Price, Robert T Steinbock, Chao Di, Katharina E Hayer, Yize Li, Christin Herrmann, Nicholas A Parenti, Jillian N Whelan, Susan R Weiss, and Matthew D Weitzman

Nucleic Acids Research, gkab896, doi:10.1093/nar/gkab896

Inefficient splicing of overlapping viral transcripts can lead to intermolecular dsRNA formation. During wildtype virus infection the presence of the E1B55K/E4orf6 viral hijacked ubiquitin ligase leads to the ubiquitination of cellular RNA binding proteins (RBPs) RALY and hnRNPC, which precludes their binding to viral RNA. In the presence of RALY and hnRNPC viral transcripts are poorly spliced, leading to the formation of dsRNA between the exonic regions of viral RNAs to the intronic regions of transcripts derived from the opposing strand. After these dsRNA molecules form, a fraction of the cytoplasmic dsRNA-sensor PKR translocates into the nucleus, where it co-localizes with viral dsRNA and is activated by auto-phosphorylation.

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