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A noncoding RNA modulator potentiates phenylalanine metabolism in mice

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A noncoding RNA modulator potentiates phenylalanine metabolism in mice. / Li, Yajuan; Tan, Zhi; Zhang, Yaohua; Zhang, Zhao; Hu, Qingsong; Liang, Ke; Jun, Yao; Ye, Youqiong; Li, Yi-Chuan; Li, Chunlai; Liao, Lan; Xu, Jianming; Xing, Zhen; Pan, Yinghong; Chatterjee, Sujash S; Nguyen, Tina K; Hsiao, Heidi; Egranov, Sergey D; Putluri, Nagireddy; Coarfa, Cristian; Hawke, David H; Gunaratne, Preethi H; Tsai, Kuang-Lei; Han, Leng; Hung, Mien-Chie; Calin, George A; Namour, Fares; Guéant, Jean-Louis; Muntau, Ania C; Blau, Nenad; Sutton, V Reid; Schiff, Manuel; Feillet, François; Zhang, Shuxing; Lin, Chunru; Yang, Liuqing.

In: SCIENCE, Vol. 373, No. 6555, 06.08.2021, p. 662-673.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, SS, Nguyen, TK, Hsiao, H, Egranov, SD, Putluri, N, Coarfa, C, Hawke, DH, Gunaratne, PH, Tsai, K-L, Han, L, Hung, M-C, Calin, GA, Namour, F, Guéant, J-L, Muntau, AC, Blau, N, Sutton, VR, Schiff, M, Feillet, F, Zhang, S, Lin, C & Yang, L 2021, 'A noncoding RNA modulator potentiates phenylalanine metabolism in mice', SCIENCE, vol. 373, no. 6555, pp. 662-673. https://doi.org/10.1126/science.aba4991

APA

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., ... Yang, L. (2021). A noncoding RNA modulator potentiates phenylalanine metabolism in mice. SCIENCE, 373(6555), 662-673. https://doi.org/10.1126/science.aba4991

Vancouver

Li Y, Tan Z, Zhang Y, Zhang Z, Hu Q, Liang K et al. A noncoding RNA modulator potentiates phenylalanine metabolism in mice. SCIENCE. 2021 Aug 6;373(6555):662-673. https://doi.org/10.1126/science.aba4991

Bibtex

@article{bb5cccac9329449baff8b58d03654ff4,
title = "A noncoding RNA modulator potentiates phenylalanine metabolism in mice",
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 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 Pah R408W/R408W mice and improved the Phe tolerance of these mice.",
author = "Yajuan Li and Zhi Tan and Yaohua Zhang and Zhao Zhang and Qingsong Hu and Ke Liang and Yao Jun and Youqiong Ye and Yi-Chuan Li and Chunlai Li and Lan Liao and Jianming Xu and Zhen Xing and Yinghong Pan and Chatterjee, {Sujash S} and Nguyen, {Tina K} and Heidi Hsiao and Egranov, {Sergey D} and Nagireddy Putluri and Cristian Coarfa and Hawke, {David H} and Gunaratne, {Preethi H} and Kuang-Lei Tsai and Leng Han and Mien-Chie Hung and Calin, {George A} and Fares Namour and Jean-Louis Gu{\'e}ant and Muntau, {Ania C} and Nenad Blau and Sutton, {V Reid} and Manuel Schiff and Fran{\c c}ois Feillet and Shuxing Zhang and Chunru Lin and Liuqing Yang",
note = "Copyright {\textcopyright} 2021, American Association for the Advancement of Science.",
year = "2021",
month = aug,
day = "6",
doi = "10.1126/science.aba4991",
language = "English",
volume = "373",
pages = "662--673",
journal = "SCIENCE",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6555",

}

RIS

TY - JOUR

T1 - A noncoding RNA modulator potentiates phenylalanine metabolism in mice

AU - Li, Yajuan

AU - Tan, Zhi

AU - Zhang, Yaohua

AU - Zhang, Zhao

AU - Hu, Qingsong

AU - Liang, Ke

AU - Jun, Yao

AU - Ye, Youqiong

AU - Li, Yi-Chuan

AU - Li, Chunlai

AU - Liao, Lan

AU - Xu, Jianming

AU - Xing, Zhen

AU - Pan, Yinghong

AU - Chatterjee, Sujash S

AU - Nguyen, Tina K

AU - Hsiao, Heidi

AU - Egranov, Sergey D

AU - Putluri, Nagireddy

AU - Coarfa, Cristian

AU - Hawke, David H

AU - Gunaratne, Preethi H

AU - Tsai, Kuang-Lei

AU - Han, Leng

AU - Hung, Mien-Chie

AU - Calin, George A

AU - Namour, Fares

AU - Guéant, Jean-Louis

AU - Muntau, Ania C

AU - Blau, Nenad

AU - Sutton, V Reid

AU - Schiff, Manuel

AU - Feillet, François

AU - Zhang, Shuxing

AU - Lin, Chunru

AU - Yang, Liuqing

N1 - Copyright © 2021, American Association for the Advancement of Science.

PY - 2021/8/6

Y1 - 2021/8/6

N2 - 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 Pah R408W/R408W mice and improved the Phe tolerance of these mice.

AB - 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 Pah R408W/R408W mice and improved the Phe tolerance of these mice.

U2 - 10.1126/science.aba4991

DO - 10.1126/science.aba4991

M3 - SCORING: Journal article

C2 - 34353949

VL - 373

SP - 662

EP - 673

JO - SCIENCE

JF - SCIENCE

SN - 0036-8075

IS - 6555

ER -