Author: Lea Gaucherand; Brittany K. Porter; Summer K. Schmaling; Christopher Harley Rycroft; Yuzo Kevorkian; Craig McCormick; Denys A. Khaperskyy; Marta Maria Gaglia
Title: The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression Document date: 2018_10_14
ID: 8k7w467p_1
Snippet: Many viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral 27 responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins 28 required for viral replication are still synthesized during shutoff. The molecular determinants of 29 target selectivity in host shutoff remain incompletely understood. Here, we report that the 30 influenza A virus shutoff factor PA-X usurps RNA s.....
Document: Many viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral 27 responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins 28 required for viral replication are still synthesized during shutoff. The molecular determinants of 29 target selectivity in host shutoff remain incompletely understood. Here, we report that the 30 influenza A virus shutoff factor PA-X usurps RNA splicing to selectively target host RNAs for 31 destruction. PA-X preferentially degrades spliced mRNAs, both transcriptome-wide and in 32 reporter assays. Moreover, proximity-labeling proteomics revealed that PA-X interacts with 33 cellular proteins involved in RNA splicing. The interaction with splicing contributes to target 34 discrimination and is unique among viral host shutoff nucleases. This novel mechanism sheds 35 light on the specificity of viral control of host gene expression and may provide opportunities for 36 development of new host-targeted antivirals. 37 38 39 All rights reserved. No reuse allowed without permission.
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