气候变化领域集成服务门户(CCPortal): A noncoding RNA modulator potentiates phenylalanine metabolism in mice

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DOI	10.1126/science.aba4991
	A noncoding RNA modulator potentiates phenylalanine metabolism in mice
	Li Y.; Tan Z.; Zhang Y.; Zhang Z.; Hu Q.; Liang K.; Jun Y.; Ye Y.; Li Y.-C.; Li C.; Liao L.; Xu J.; Xing Z.; Pan Y.; Chatterjee S.S.; Nguyen T.K.; Hsiao H.; Egranov S.D.; Putluri N.; Coarfa C.; Hawke D.H.; Gunaratne P.H.; Tsai K.-L.; Han L.; Hung M.-C.; Calin G.A.; Namour F.; Guéant J.-L.; Muntau A.C.; Blau N.; Sutton V.R.; Schiff M.; Feillet F.; Zhang S.; Lin C.; Yang L.
发表日期	2021
ISSN	0036-8075
起始页码	662
结束页码	673
卷号	373 期号:6555
英文摘要	The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc-HULC mimics reduced excessive Phe in Pair−/− and PahR408W/R408W mice and improved the Phe tolerance of these mice. © 2021 American Association for the Advancement of Science. All rights reserved.
英文关键词	long untranslated RNA; long untranslated RNA HULC; long untranslated RNA Pair; n acetylgalactosamine; phenylalanine; phenylalanine 4 monooxygenase; RNA derivative; sapropterin; unclassified drug; untranslated RNA mimic; biopterin; HULC long non-coding RNA, human; long untranslated RNA; phenylalanine; phenylalanine 4 monooxygenase; protein binding; sapropterin; amino acid; enzyme activity; metabolism; PAH; RNA; rodent; amino acid blood level; amino acid metabolism; animal experiment; animal model; animal tissue; Article; cell differentiation; controlled study; disease model; drug potentiation; enzyme activity; enzyme substrate; female; growth retardation; hypopigmentation; induced pluripotent stem cell; knockout mouse; liquid chromatography-mass spectrometry; liver cell; male; mouse; neurologic disease; nonhuman; phenylketonuria; protein depletion; protein interaction; seizure; animal; chemistry; conformation; diet; embryology; genetics; human; liver; metabolism; phenylketonuria; Acetylgalactosamine; Animals; Biopterin; Diet; Disease Models, Animal; Female; Hepatocytes; Humans; Liver; Male; Mice; Mice, Knockout; Nucleic Acid Conformation; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Protein Binding; RNA, Long Noncoding
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/244535
作者单位	Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, United States; Intelligent Molecular Discovery Laboratory, Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77054, United States; Department of Biochemistry and Molecular Biology, The University of Texas, Health Science Center, Houston McGovern Medical School, Houston, TX 77030, United States; Genetically Engineered Mouse Core, Advanced Technology Cores, Baylor College of Medicine, Houston, TX 77030, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States; Department of Biochemistry and Biology, University of Houston, Houston, TX 77030, United States; Department of Systems Biology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, United States; Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M ...
推荐引用方式 GB/T 7714	Li Y.,Tan Z.,Zhang Y.,et al. A noncoding RNA modulator potentiates phenylalanine metabolism in mice[J],2021,373(6555).
APA	Li Y..,Tan Z..,Zhang Y..,Zhang Z..,Hu Q..,...&Yang L..(2021).A noncoding RNA modulator potentiates phenylalanine metabolism in mice.Science,373(6555).
MLA	Li Y.,et al."A noncoding RNA modulator potentiates phenylalanine metabolism in mice".Science 373.6555(2021).