气候变化领域集成服务门户(CCPortal): Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs

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DOI	10.1073/PNAS.2016289118
	Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs
	Ku Y.; Park J.-H.; Cho R.; Lee Y.; Park H.-M.; Kim M.A.; Hur K.; Byun S.Y.; Liu J.; Lee Y.-S.; Shum D.; Shin D.-Y.; Koh Y.; Cho J.-Y.; Yoon S.-S.; Hong J.; Kim Y.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA demethylation; Double-stranded RNAs; Noncoding RNA; Posttranscriptional regulation; RNA-binding protein
语种	英语
scopus关键词	binding protein; double stranded RNA; long untranslated RNA; Staufen 1; TINCR RNA; unclassified drug; viral protein; virus RNA; Article; cell death; controlled study; DNA methylation; immune response; nonhuman; priority journal; protein expression; protein localization; protein RNA binding; real time polymerase chain reaction; Retroviridae; RNA degradation; RNA stability; sequence analysis; virus genome
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180048
作者单位	Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea; KAIST Institute for Health Science and Technology (KIHST), KAIST, Daejeon, 34141, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 03080, South Korea; Cancer Research Institute, Seoul National University Hospital, Seoul, 03080, South Korea; Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea; Screening Discovery Platform, Translation Research Division, Institut Pasteur Korea, Gyeonggi, 13488, South Korea; Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, South Korea
推荐引用方式 GB/T 7714	Ku Y.,Park J.-H.,Cho R.,et al. Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs[J],2021,118(13).
APA	Ku Y..,Park J.-H..,Cho R..,Lee Y..,Park H.-M..,...&Kim Y..(2021).Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Ku Y.,et al."Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).