title: Amplified RLR signaling activation through an interferon-stimulated gene-endoplasmic reticulum stress-mitochondrial calcium uniporter protein loop.
abstract: Type I interferon (IFN-I) is critical for a host against viral and bacterial infections via induction of hundreds of interferon-stimulated genes (ISGs), but the mechanism underlying the regulation of IFN-I remains largely unknown. In this study, we first demonstrate that ISG expression is required for optimal IFN-β levels, an effect that is further enhanced by endoplasmic reticulum (ER) stress. Furthermore, we identify mitochondrial calcium uniporter protein (MCU) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein that is important for ER stress induction and amplified MAVS signaling activation. In addition, by performing an ectopic expression assay to screen a library of 117 human ISGs for effects on IFN-β levels, we found that tumor necrosis factor receptor 1 (TNFR1) significantly increases IFN-β levels independent of ER stress. Altogether, our findings suggest that MCU and TNFR1 are involved in the regulation of RIG-I-like receptors (RLR) signaling.
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Cheng
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|The College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yajin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|The College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lujun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shengyi
authors.initials: S
authors.lastname: Peng
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D015870:Gene Expression; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015220:Calcium Channels; D053487:DEAD-box RNA Helicases; D050835:Interferon Regulatory Factors; D016899:Interferon-beta; D047888:Receptors, Tumor Necrosis Factor, Type I; C512612:MAVS protein, mouse; C034703:mitochondrial calcium uniporter