Talk abstracts
Talk on Saturday 11:15-11:30am submitted by Sarah Venus
Vaccinia virus K7 protein inhibits biochemical activities and liquid-liquid phase separation of the DEAD-box RNA helicase DDX3X
Sarah Venus (Center for RNA Science and Therapeutics, Case Western Reserve University), Kaba Tandjigora (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 the vaccinia virus K7 protein. 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. Here we show that K7 inhibits the ATP-dependent RNA unwinding and ATP hydrolysis activities of DDX3X. We further show that K7 impairs the formation of recombinant DDX3X phase-separated droplets in vitro, as well as DDX3X-containing stress granules within human cells. Our data reveal that the targeting of the intrinsically disordered N-terminus of DDX3X is an effective way to interfere with both of the disparate functions of DDX3X, its ability to resolve RNA structure and its association with stress granules. Our findings provide new mechanistic insight into strategies by which viruses target DDX3X to alter RNA metabolism in the host.
Keywords: DDX3X, stress granule, vaccinia