TY - JOUR
T1 - The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs
AU - Esclatine, Audrey
AU - Taddeo, Brunella
AU - Roizman, Bernard
PY - 2004/12/28
Y1 - 2004/12/28
N2 - The UL41 protein of herpes simplex virus 1 has been reported to mediate the degradation of both viral and cellular mRNAs. Extensive studies on β-actin and some viral mRNAs were consonant with this conclusion. In earlier studies, we reported that the UL41-dependent degradation of cellular mRNAs up-regulated after infection was selective. One class of the up-regulated mRNAs, ex-emplified by the stress-inducible immediate-early 1 mRNA, is deadenylated, 3′ to 5′ degraded and is not translated. Another class of up-regulated mRNAs, exemplified by GADD45β, does not undergo this pattern of degradation and is translated. A puzzling feature of the earlier results is that the amounts of up-regulated mRNAs accumulating in the cytoplasm of ΔUL41 mutant virus-infected cells was lower than in WT virus-infected cells, a contradiction, inasmuch as if the rates of accumulation were identical and degradation of the mRNAs were higher in WT virus-infected cells, the steady-state levels should have been higher in ΔUL41 mutant virus-infected cells. In this report, we show that in ΔU L41 mutant virus-infected cells, the rates of degradation of the stress-inducible immediate-early response gene 1 and other up-regulated mRNAs are approximately the same as those observed in mock-infected cells and are faster than in WT virus-infected cells. This is contrary to the observed U L41-dependent degradation of β-actin and other mRNAs. The U L41 protein thus mediates two functions, i.e., it mediates rapid degradation of some mRNAs exemplified by β-actin and stabilizes or delays the degradation of other mRNAs exemplified by GADD45β, tristetraprolin, etc. A model unifying both activities of the UL41 protein is presented.
AB - The UL41 protein of herpes simplex virus 1 has been reported to mediate the degradation of both viral and cellular mRNAs. Extensive studies on β-actin and some viral mRNAs were consonant with this conclusion. In earlier studies, we reported that the UL41-dependent degradation of cellular mRNAs up-regulated after infection was selective. One class of the up-regulated mRNAs, ex-emplified by the stress-inducible immediate-early 1 mRNA, is deadenylated, 3′ to 5′ degraded and is not translated. Another class of up-regulated mRNAs, exemplified by GADD45β, does not undergo this pattern of degradation and is translated. A puzzling feature of the earlier results is that the amounts of up-regulated mRNAs accumulating in the cytoplasm of ΔUL41 mutant virus-infected cells was lower than in WT virus-infected cells, a contradiction, inasmuch as if the rates of accumulation were identical and degradation of the mRNAs were higher in WT virus-infected cells, the steady-state levels should have been higher in ΔUL41 mutant virus-infected cells. In this report, we show that in ΔU L41 mutant virus-infected cells, the rates of degradation of the stress-inducible immediate-early response gene 1 and other up-regulated mRNAs are approximately the same as those observed in mock-infected cells and are faster than in WT virus-infected cells. This is contrary to the observed U L41-dependent degradation of β-actin and other mRNAs. The U L41 protein thus mediates two functions, i.e., it mediates rapid degradation of some mRNAs exemplified by β-actin and stabilizes or delays the degradation of other mRNAs exemplified by GADD45β, tristetraprolin, etc. A model unifying both activities of the UL41 protein is presented.
KW - AU-rich elements
KW - Nucleases
KW - Virion host shutoff
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U2 - 10.1073/pnas.0408272102
DO - 10.1073/pnas.0408272102
M3 - Article
C2 - 15596716
AN - SCOPUS:11144223347
SN - 0027-8424
VL - 101
SP - 18165
EP - 18170
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -