RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2021-06-01
|
| Series: | Journal of Integrative Neuroscience |
| Subjects: | |
| Online Access: | https://jin.imrpress.com/fileup/1757-448X/PDF/1625014726269-1554335725.pdf |
| _version_ | 1828341367522197504 |
|---|---|
| author | John Agbo Akinsola Raphael Akinyemi Dingfeng Li Qingyang Zhang Xiaohui Li Wenbo Li Juan Zhang Qiang Liu |
| author_facet | John Agbo Akinsola Raphael Akinyemi Dingfeng Li Qingyang Zhang Xiaohui Li Wenbo Li Juan Zhang Qiang Liu |
| author_sort | John Agbo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T23:12:58Z |
| format | Article |
| id | doaj.art-4bde9dda93714e53ac103c55a1d0c99a |
| institution | Directory Open Access Journal |
| issn | 1757-448X |
| language | English |
| last_indexed | 2024-04-13T23:12:58Z |
| publishDate | 2021-06-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-4bde9dda93714e53ac103c55a1d0c99a2022-12-22T02:25:31ZengIMR PressJournal of Integrative Neuroscience1757-448X2021-06-0120226527610.31083/j.jin20020261625014726269-1554335725RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCRJohn Agbo0Akinsola Raphael Akinyemi1Dingfeng Li2Qingyang Zhang3Xiaohui Li4Wenbo Li5Juan Zhang6Qiang Liu7Institute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaRecent 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.https://jin.imrpress.com/fileup/1757-448X/PDF/1625014726269-1554335725.pdfheterogeneous nuclear ribonucleoprotein3-hydroxy-3-methyl-glutaryl-coenzyme a reductaseneuronal cholesterol biosynthesisneuroblastoma cellmn1 cellrna metabolism |
| spellingShingle | John Agbo Akinsola Raphael Akinyemi Dingfeng Li Qingyang Zhang Xiaohui Li Wenbo Li Juan Zhang Qiang Liu RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR Journal of Integrative Neuroscience heterogeneous nuclear ribonucleoprotein 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase neuronal cholesterol biosynthesis neuroblastoma cell mn1 cell rna metabolism |
| title | RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR |
| title_full | RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR |
| title_fullStr | RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR |
| title_full_unstemmed | RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR |
| title_short | RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR |
| title_sort | rna binding protein hnrnpr reduces neuronal cholesterol levels by binding to and suppressing hmgcr |
| topic | heterogeneous nuclear ribonucleoprotein 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase neuronal cholesterol biosynthesis neuroblastoma cell mn1 cell rna metabolism |
| url | https://jin.imrpress.com/fileup/1757-448X/PDF/1625014726269-1554335725.pdf |
| work_keys_str_mv | AT johnagbo rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT akinsolaraphaelakinyemi rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT dingfengli rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT qingyangzhang rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT xiaohuili rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT wenboli rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT juanzhang rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr AT qiangliu rnabindingproteinhnrnprreducesneuronalcholesterollevelsbybindingtoandsuppressinghmgcr |