Lh. Nguyen et al., The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro, BIOCHEM, 40(24), 2001, pp. 7174-7179
The human ISG20/HEM45 gene was identified independently on the basis of its
increased level of expression in response to either interferon or estrogen
hormone. Notably, the encoded protein is homologous with members of the 3'
to 5' exonuclease superfamily that includes RNases T and D, and the proofr
eading domain of Escherichia coli DNA polymerase I. We provide here direct
biochemical evidence that Isg20 acts as a 3' to 5' exonuclease in vitro. Th
is protein displays a pH optimum of similar to7.0, prefers Mn2+ as a metal
cofactor, and degrades RNA at a rate that is similar to 35-fold higher than
its rate for single-stranded DNA. Along with RNase L, Isg20 is the second
known RNase regulated by interferon. Previous data showed that Isg20 is loc
ated in promyelocytic leukemia (PML) nuclear bodies, known sites of hormone
-dependent RNA polymerase II transcription and oncogenic DNA viral transcri
ption and replication. The combined data suggest a potential role for Isg20
in degrading viral RNAs as part of the interferon-regulated antiviral resp
onse and/or cellular mRNAs as a regulatory component of interferon and estr
ogen signaling.