{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li Y"],"funding":["The University of Texas MD Anderson Cancer Center","U.S. Department of Defense","National Cancer Institute","NCI NIH HHS","National Institutes of Health","National Research University Fund","Cancer Prevention and Research Institute of Texas","American Association for Cancer Research","NIH HHS","National Science Foundation","Andrew Sabin Family Foundation"],"pagination":["662-673"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9714245"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["373(6555)"],"pubmed_abstract":["The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA <i>Pair</i> and human <i>HULC</i> associate with phenylalanine hydroxylase (PAH). <i>Pair</i>-knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. <i>HULC</i> depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell-differentiated hepatocytes. Mechanistically, <i>HULC</i> modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we "],"journal":["Science (New York, N.Y.)"],"pubmed_title":["A noncoding RNA modulator potentiates phenylalanine metabolism in mice."],"pmcid":["PMC9714245"],"funding_grant_id":["S10 OD012304","CA218025-01","P30CA125123","R01 CA218036","180259","RP170333","R01 CA231011","CHE-1411859","MINOR CORE 17","CA218036-01","R01 CA220297","R01CA225955","BC180196","BC181384","RP200423","R01 CA218025","RP170005","R01 CA216426","CA231011-01","P30 CA125123","RP150085","RP190570","2018","P30 CA016672","20-60-51 Yang","1S10OD012304-01","R01 CA225955","Institutional Research Grant"],"pubmed_authors":["Gunaratne PH","Han L","Hsiao H","Ye Y","Zhang S","Putluri N","Liao L","Namour F","Jun Y","Tsai KL","Feillet F","Liang K","Nguyen TK","Xing Z","Pan Y","Li C","Yang L","Coarfa C","Schiff M","Muntau AC","Xu J","Gueant JL","Li Y","Li YC","Egranov SD","Blau N","Lin C","Zhang Z","Hung MC","Tan Z","Zhang Y","Sutton VR","Calin GA","Hawke DH","Hu Q","Chatterjee SS"],"additional_accession":[]},"is_claimable":false,"name":"A noncoding RNA modulator potentiates phenylalanine metabolism in mice.","description":"The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA <i>Pair</i> and human <i>HULC</i> associate with phenylalanine hydroxylase (PAH). <i>Pair</i>-knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. <i>HULC</i> depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell-differentiated hepatocytes. Mechanistically, <i>HULC</i> modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2026-05-28T21:29:03.929Z","creation":"2025-04-19T22:49:56.466Z"},"accession":"S-EPMC9714245","cross_references":{"pubmed":["34353949"],"doi":["10.1126/science.aba4991"]}}