Intact JAK-STAT signaling pathway is a prerequisite for STAT1 to reinforce the expression of RIG-G gene.
We previously reported that IRF-9/STAT2 functional interaction could drive the expression of retinoic acid-induced gene G (RIG-G), independently of STAT1 and the classical JAK-STAT pathway, providing a novel alternative pathway for interferons (IFN) to mediate their multiple biological properties. In addition, we also found that IRF-1 could regulate RIG-G induction as well as the expression of IRF-9 and STAT2 in some cases. But the mechanisms by which IRF-1 exerted its action remained to be elucidated. Here, we showed that STAT1 could significantly enhance the effects of the IRF-9/STAT2 complex or IRF-1 on RIG-G induction through an activated JAK-STAT pathway, though it was not essential for RIG-G expression. In STAT1-deficient U3A cells, IRF-1 could induce RIG-G expression via the IFN-stimulated response elements in the RIG-G gene promoter, but it failed to upregulate IRF-9 and STAT2 unless the U3A cells were reconstituted by exogenous STAT1. In STAT1-expressing cells, IRF-1 indirectly activated RIG-G expression through an IRF-9/STAT2-dependent manner. Taken together, we concluded that the expression of RIG-G was independent on the classical JAK-STAT pathway, but could be greatly increased by it. This work will be of great benefit to us for a better understanding of the mechanisms on RIG-G gene expression regulation.
Shanghai Institute of Hematology and State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road II, Shanghai 200025, China.
Ye-Jiang
YJ
Lou
Zhang-Lin
ZL
Zhang
Xiao-Rong
XR
Pan
Gui-Ping
GP
Xu
Pei-Min
PM
Jia
Dong
D
Li
Jian-Hua
JH
Tong
D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053612:Janus Kinases / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
C116468:IFIT3 protein, human; C494227:IRF9 protein, human; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D047908:Intracellular Signaling Peptides and Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D053612:Janus Kinases