RT Journal Article
SR Electronic
T1 The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 442996
DO 10.1101/442996
A1 Lea Gaucherand
A1 Brittany K. Porter
A1 Summer K. Schmaling
A1 Christopher Harley Rycroft
A1 Yuzo Kevorkian
A1 Craig McCormick
A1 Denys A. Khaperskyy
A1 Marta Maria Gaglia
YR 2018
UL http://biorxiv.org/content/early/2018/10/14/442996.abstract
AB Many viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins required for viral replication are still synthesized during shutoff. The molecular determinants of target selectivity in host shutoff remain incompletely understood. Here, we report that the influenza A virus shutoff factor PA-X usurps RNA splicing to selectively target host RNAs for destruction. PA-X preferentially degrades spliced mRNAs, both transcriptome-wide and in reporter assays. Moreover, proximity-labeling proteomics revealed that PA-X interacts with cellular proteins involved in RNA splicing. The interaction with splicing contributes to target discrimination and is unique among viral host shutoff nucleases. This novel mechanism sheds light on the specificity of viral control of host gene expression and may provide opportunities for development of new host-targeted antivirals.