p72 DEAD box RNA helicase is required for optimal
function of the zinc-finger antiviral protein
http://www.pnas.org/content/105/11/4352.full.pdf#page=1&view=FitH
4352?4357 PNAS March 18, 2008 vol. 105 no. 11
The zinc-finger antiviral protein (ZAP) specifically inhibits the
replication of many viruses by preventing the accumulation of viral
mRNAs in the cytoplasm. ZAP directly binds to the viral mRNAs and
recruits the RNA exosome to degrade the target RNA. In the
present study, we identified the p72 DEAD box RNA helicase, but
not the highly similar RNA helicase p68, as a ZAP-interacting
protein. The binding domain of ZAP was mapped to its N-terminal
portion, whereas both the N- and C-terminal domains of p72 bound
to ZAP. Overexpression of the C-terminal domain of p72 reduced
ZAP?s activity, whereas overexpression of the full-length p72
enhanced ZAP?s activity. The RNA helicase activity was required for
p72 to promote ZAP-mediated RNA degradation. Depletion of p72
by RNAi also reduced ZAP?s activity but did not affect tristetrapro-
lin-mediated RNA degradation. We conclude that p72 is required
for the optimal activity of ZAP, and we propose that p72 helps to
restructure the ZAP-bound target mRNA for efficient degradation.
function of the zinc-finger antiviral protein
http://www.pnas.org/content/105/11/4352.full.pdf#page=1&view=FitH
4352?4357 PNAS March 18, 2008 vol. 105 no. 11
The zinc-finger antiviral protein (ZAP) specifically inhibits the
replication of many viruses by preventing the accumulation of viral
mRNAs in the cytoplasm. ZAP directly binds to the viral mRNAs and
recruits the RNA exosome to degrade the target RNA. In the
present study, we identified the p72 DEAD box RNA helicase, but
not the highly similar RNA helicase p68, as a ZAP-interacting
protein. The binding domain of ZAP was mapped to its N-terminal
portion, whereas both the N- and C-terminal domains of p72 bound
to ZAP. Overexpression of the C-terminal domain of p72 reduced
ZAP?s activity, whereas overexpression of the full-length p72
enhanced ZAP?s activity. The RNA helicase activity was required for
p72 to promote ZAP-mediated RNA degradation. Depletion of p72
by RNAi also reduced ZAP?s activity but did not affect tristetrapro-
lin-mediated RNA degradation. We conclude that p72 is required
for the optimal activity of ZAP, and we propose that p72 helps to
restructure the ZAP-bound target mRNA for efficient degradation.