The human interferon-regulated ISG95 protein interacts with RNA polymerase II and shows methyltransferase activity.
A major mechanism of cellular resistance to viral invasion involves genes from the interferon signaling pathway, called ISGs (interferon stimulated genes). Global transcriptional profiling studies have linked increased expression of ISG95 (KIAA0082) to response to interferon treatment and viral infection, suggesting that it may be part of the cellular defense against viral replication. In this work, we show that the ISG95 promoter can drive interferon-induced transcription of a reporter gene in Vero cells. Recombinant ISG95 shows RNA- and S-adenosyl-methionine binding and protein methyltransferase activity in vitro. ISG95 interacts with the C-terminal domain of RNA polymerase II, which is consistent with its nuclear localization and with the predicted function of the WW domain found in the C-terminal region of ISG95. The results presented in this work indicate that ISG95 is part of the interferon response pathway and functions in the pre-mRNA processing events mediated by the C-terminal domain of the RNA polymerase II.
Center for Structural Molecular Biology, Brazilian Synchrotron Light Laboratory, LNLS P.O. Box 6192, CEP 13080-970, Campinas SP, Brazil.
Thais
T
Haline-Vaz
Tereza Cristina Lima
TC
Silva
Nilson I T
NI
Zanchin
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D006801:Humans; D007372:Interferons / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D012333:RNA, Messenger; D011994:Recombinant Proteins; D007372:Interferons; C530219:CMTR1 protein, human; D008780:Methyltransferases; D012319:RNA Polymerase II