Poster abstracts
Poster number 150 submitted by Sarah Venus
Interactions with Vaccinia Virus K7 Protein Alter the Biochemical Activity of the DEAD-Box RNA Helicase DDX3X
Sarah Venus (Center for RNA Science and Therapeutics, Case Western Reserve University), McKenzie Clapp (Center for RNA Science and Therapeutics, Case Western Reserve University), Andrea Putnam (Center for RNA Science and Therapeutics, Case Western Reserve University), Eckhard Jankowsky (Center for RNA Science and Therapeutics, Case Western Reserve University)
Abstract:
The DEAD-box RNA helicase DDX3X, which functions in translation initiation and cellular signaling, is targeted by proteins from diverse viruses, including K7, a protein from the poxvirus vaccinia. K7 binds the N-terminus of DDX3X, a region that facilitates DDX3X association with translation initiation factors and stress granules. While interactions between K7 and DDX3X are thought to disrupt immune signaling pathways, the impact of K7 on DDX3X’s biochemical activities and roles in RNA metabolism is unknown. We show that K7 inhibits both the ATP-dependent RNA duplex unwinding and ATP hydrolysis activities of DDX3X. We further show that K7 impairs the formation of recombinant DDX3X phase-separated droplets in vitro, suggesting that K7 may impact the formation of DDX3X-containing stress granules within cells. As both DDX3X’s ability to resolve RNA secondary structure and its association with stress granules influence DDX3X’s role in translation initiation, characterizing the interaction between K7 and DDX3X provides mechanistic insight into strategies by which viruses target DDX3X to alter RNA metabolism in the host.
Keywords: DEAD-box RNA helicase , DDX3X