Anti-tumor necrosis factor(TNF)therapy for inflammatory bowel disease(IBD)is hampered by issues of nonresponse and resistance,highlighting the urgent need for alternative or complementary treatments.Our study revealed...Anti-tumor necrosis factor(TNF)therapy for inflammatory bowel disease(IBD)is hampered by issues of nonresponse and resistance,highlighting the urgent need for alternative or complementary treatments.Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients,which was inversely related to the severity of the disease.A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin,a nuclease that degrades mitochondrial RNA,which is known to amplify inflammatory responses.By degrading mitochondrial RNA,angiogenin inhibits the inflammatory response in macrophages,suggesting a potent immune-modulatory role for taurine.This mechanism implies that taurine could serve as an adjunct to anti-TNF therapies,enhancing their efficacy and providing a novel strategy for the management of IBD and other chronic inflammatory diseases by harnessing the body's innate immune regulatory mechanisms.展开更多
Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that ...Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space （IMS） and the IMS- localized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.展开更多
基金supported by the distinguished Young Scientist Fund of NSFC(82125016)the National Natural Science Foundation of China,and the Key Program(82230061)+6 种基金This research was supported by the National Natural Science Foundation of China,Special Program(82341216)This study was also supported by the National Natural Science Foundation of China(82071046,82100540,82341215,82370531,82300581)the Jiangsu Science and Technology Project(Social Development)(BE2019669)the Natural Science Foundation of Zhejiang Province(LQ24H030005)This project is supported by the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.82202019)The project was supported by the China Postdoctoral Science Foundation(Grant No.2022M723664/2023M734007)supported by the 111 Program(D20036).
文摘Anti-tumor necrosis factor(TNF)therapy for inflammatory bowel disease(IBD)is hampered by issues of nonresponse and resistance,highlighting the urgent need for alternative or complementary treatments.Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients,which was inversely related to the severity of the disease.A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin,a nuclease that degrades mitochondrial RNA,which is known to amplify inflammatory responses.By degrading mitochondrial RNA,angiogenin inhibits the inflammatory response in macrophages,suggesting a potent immune-modulatory role for taurine.This mechanism implies that taurine could serve as an adjunct to anti-TNF therapies,enhancing their efficacy and providing a novel strategy for the management of IBD and other chronic inflammatory diseases by harnessing the body's innate immune regulatory mechanisms.
基金We thank Haiteng Deng for the help on Mass Spec and Zhi Lu and Hongwei Wang for discussion. This research was supported by the Priority Research Program of the Ministry of Science and Technology 2017YFA0504600, the National Natural Science Foundation of China （Grant Nos. 31371439 and 91649103）, and Ministry of Education 1000 youth program.
文摘Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space （IMS） and the IMS- localized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.
