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RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR

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机构： [1]Institute of Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 230001 Hefei, Anhui, China. [2]Neurodegenerative Disease Research Center, University of Science and Technology of China, 230026 Hefei, Anhui, China. [3]CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, 230026 Hefei, Anhui, China. [4]National Synchrotron Radiation Laboratory, University of Science and Technology of China, 230029 Hefei, Anhui, China. [5]CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, Yunnan, China.

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Recent studies have identified multiple RNA-binding proteins tightly associated with lipid and neuronal cholesterol metabolism and cardiovascular disorders. However, the role of heterogeneous nuclear ribonucleoprotein R (hnRNPR) in cholesterol metabolism and homeostasis, whether it has a role in regulating 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), is largely unknown. This research identifies hnRNPR as a repressor of HMGCR. Knockdown and overexpression of hnRNPR in cultured neuroblastoma cell (N2a) and MN1 cell lines enhances and inhibits HMGCR in vitro, respectively. hnRNPR may exert its repressive activity on HMGCR mRNA and protein levels by using its RNA recognition motif (RRM) in recognizing and modulating the stability of HMGCR transcript. Our RNA immunoprecipitation and luciferase reporter assays demonstrate a direct interaction between hnRNPR and HMGCR mRNA. We also demonstrated that hnRNR binds to the 3' untranslated region (3' UTR) of HMGCR and reduces its translation, while hnRNPR silencing increases HMGCR expression and cholesterol levels in MN1 and N2a cells. Overexpression of HMGCR significantly restores the decreased cholesterol levels in hnRNPR administered cells. Taken together, we identify hnRNPR as a novel post-transcriptional regulator of HMGCR expression in neuronal cholesterol homeostasis.© 2021 The Author(s). Published by IMR Press.

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出版当年[2021]版：

大类 | 4 区医学

小类 | 4 区神经科学

最新[2023]版：

大类 | 4 区医学

小类 | 4 区神经科学

第一作者：

第一作者机构： [1]Institute of Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 230001 Hefei, Anhui, China. [2]Neurodegenerative Disease Research Center, University of Science and Technology of China, 230026 Hefei, Anhui, China. [3]CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, 230026 Hefei, Anhui, China.

通讯作者：

通讯机构： [1]Institute of Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 230001 Hefei, Anhui, China. [2]Neurodegenerative Disease Research Center, University of Science and Technology of China, 230026 Hefei, Anhui, China. [3]CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, 230026 Hefei, Anhui, China. [5]CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, Yunnan, China.

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