title: SRSF1 facilitates cytosolic DNA-induced production of type I interferons recognized by RIG-I.
abstract: BACKGROUND
  Evidence has shown that psoriasis is closely associated with infection; however, the mechanism of this association remains unclear. In mammalian cells, viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is also highly upregulated in psoriatic lesions and is responsible for IFN production. However, RIG-I mediated regulatory signaling in psoriasis is poorly understood.
  
  
  METHODS
  We screened a cDNA library and identified potential RIG-I interacting partners that may play a role in psoriasis.
  
  
  RESULTS
  We found that serine/arginine-rich splicing factor 1 (SRSF1) could specifically interact with RIG-I to facilitate RIG-I mediated production of type-I IFN that is triggered by cytosolic DNA. We found SRSF1 associates with RNA polymerase III and RIG-I in a DNA-dependent manner. In addition, treatment with a TNFα inhibitor downregulated SRSF1 expression in peripheral blood mononuclear cells (PBMCs) from psoriasis vulgaris patients.
  
  
  CONCLUSIONS
  Based on the abundance of pathogenic cytosolic DNA that is detected in psoriatic lesions, our finding that RIG-I interacts with SRSF1 to regulate type-I IFN production reveals a critical link regarding how cytosolic DNA specifically activates aberrant IFN expression. These data may provide new therapeutic targets for the treatment of psoriasis.
authors: Laboratory of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Feng
authors: F
authors: Xue
authors: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Xia
authors: X
authors: Li
authors: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Xiaoqing
authors: X
authors: Zhao
authors: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Lanqi
authors: L
authors: Wang
authors: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Min
authors: M
authors: Liu
authors: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Ruofei
authors: R
authors: Shi
authors: Laboratory of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Jie
authors: J
authors: Zheng
mesh_terms: D003600:Cytosol / Q000378:metabolism* / Q000473:pathology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011971:Receptors, Immunologic; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D011971:Receptors, Immunologic; C000595779:SRSF1 protein, human; D000068103:Serine-Arginine Splicing Factors; D007371:Interferon-gamma; D004247:DNA; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases