The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response.

The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression. Mechanistically, RNF185 specifically catalyzed the K27-linked poly-ubiquitination of cGAS, which promoted its enzymatic activity. Additionally, Systemic Lupus Erythematosus (SLE) patients displayed elevated expression of RNF185 mRNA. Collectively, this study uncovers RNF185 as the first E3 ubiquitin ligase of cGAS, shedding light on the regulation of cGAS activity in innate immune responses.

MicroRNA-590 is an EMT-suppressive microRNA involved in the TGFß signaling pathway.

Over the last few decades, the epithelial-to-mesenchymal transition (EMT) has been identified as being involved in a number of aspects of physiological processes and various pathological events, including embryonic development and renal fibrosis. Transforming growth factor­ß receptor 2 (TGFßR2) is a widely studied gene, which fulfils a vital role in the TGFß signaling pathway and exerts a crucial function in the progression of EMT. Previous studies demonstrated that the dysregulation of microRNAs (miRNAs) is considered to be associated with the EMT process. However, the precise functional involvement of miRNAs in EMT remains to be fully elucidated. In the present study, the level of miR­590 was decreased in an EMT model in vitro and in vivo. Furthermore, the overexpression of miR­590 inhibited EMT by upregulating the epithelial marker, E­cadherin, and downregulating the mesenchymal markers, laminin, α­smooth muscle actin (α­SMA) and collagen, in the human kidney 2 (HK2) cell line. Furthermore, TGFßR2 was negatively regulated by miR­590. In addition, performing a knockdown of TGFßR2 with small­interfering RNA had an effect similar to miR­590 on EMT in the HK2 cell line, whereas the transfection of pCMV­tag2B­TGFßR2 reversed the effect of miR­590 on EMT in HK2 cells. Taken together, the present study demonstrated that miR-590 is a novel EMT-suppressive microRNA, which targets TGFßR2.