[Study on mechanisms of the expression regulation of interferon-induced gene RIG-G].
OBJECTIVE
To investigate the molecular mechanisms of the expression regulation of retinoic acidinduced gene G (RIG-G) by interferon alpha (IFNalpha).


METHODS
RIG-G promoter region was analyzed by bioinformatics. The functional activities of RIG-G promoter with or without IFNalpha were detected by luciferase reporter assay and electrophoretic mobility shift assay (EMSA).


RESULTS
RIG-G promoter region contained two well-conserved IFN-stimulated response elements (ISREs). Both ISRE I and ISRE II showed their effective binding abilities with signal transducer and activator of transcription 1 (STAT1). In HT1080 cells, in contrast with the empty plasmid pXP2, pXP2-A reporter construct containing intact ISRE I and ISRE II showed a significant higher baseline expression (1741.2 +/- 517.5) which could be further enhanced up to three-four folds by IFNalpha (5338.7 +/- 1226.9, P < 0.05). However, the luciferase activity of pXP2-A as well as its IFNalpha inducibility could be abrogated in STAT1-deficient U3A cells (from 1741.2 +/- 517.5 to 406.1 +/- 103.2, P < 0.05), indicating that the STAT1 protein was a prerequisite for the activities of ISRE I and ISRE II.


CONCLUSIONS
ISREs present in RIG-G promoter region are molecular basis of IFNalpha induced RIG-G expression. RIG-G is a target gene directly regulated by STAT1 protein and should play a key role in IFNalpha signaling pathways.
Li
Dong
D
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025 PR China.
Xiao
Shu
S
Pan
Xiao-rong
XR
Lou
Ye-jiang
YJ
Jia
Pei-min
PM
Tong
Jian-hua
JH
D001483:Base Sequence; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology* / Q000502:physiology; D007372:Interferons / Q000502:physiology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000378:metabolism*
D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; D007372:Interferons