Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells

Abstract Oxygen shortage, known as hypoxia, occurs commonly in both physiological and pathological conditions. Transcriptional regulation by hypoxia-inducible factors is a dominant regulatory mechanism controlling hypoxia-responsive genes during acute hypoxia; however, recent studies suggest that po...

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Main Authors: Yoko Ogura, Xiaoning Sun, Zaijun Zhang, Kentaro Kawata, Jinyu Wu, Ryuma Matsubara, Atsuko Nakanishi Ozeki, Kenzui Taniue, Rena Onoguchi-Mizutani, Shungo Adachi, Koh Nakayama, Nobuhito Goda, Nobuyoshi Akimitsu
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-91828-w
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author Yoko Ogura
Xiaoning Sun
Zaijun Zhang
Kentaro Kawata
Jinyu Wu
Ryuma Matsubara
Atsuko Nakanishi Ozeki
Kenzui Taniue
Rena Onoguchi-Mizutani
Shungo Adachi
Koh Nakayama
Nobuhito Goda
Nobuyoshi Akimitsu
author_facet Yoko Ogura
Xiaoning Sun
Zaijun Zhang
Kentaro Kawata
Jinyu Wu
Ryuma Matsubara
Atsuko Nakanishi Ozeki
Kenzui Taniue
Rena Onoguchi-Mizutani
Shungo Adachi
Koh Nakayama
Nobuhito Goda
Nobuyoshi Akimitsu
author_sort Yoko Ogura
collection DOAJ
description Abstract Oxygen shortage, known as hypoxia, occurs commonly in both physiological and pathological conditions. Transcriptional regulation by hypoxia-inducible factors is a dominant regulatory mechanism controlling hypoxia-responsive genes during acute hypoxia; however, recent studies suggest that post-transcriptional regulation, including RNA degradation, also involves hypoxia-induced gene expression during the chronic hypoxia. In this study, we developed a method to quantify the contributions of RNA synthesis and degradation to differential gene expression, and identified 102 genes mainly regulated via RNA degradation under chronic hypoxia in HCT116 cells. Bioinformatics analysis showed that the genes mainly regulated by RNA degradation were involved in glycolysis. We examined changes in the RNA-binding ability of RNA-binding proteins by RNA interactome capture and statistical analysis using public databases. We identified fragile X messenger ribonucleoprotein 1 (FMRP) as an RNA-binding protein involved in the chronic hypoxia-induced increase in mRNAs encoding rate-limiting enzymes. This study emphasizes the importance of post-transcriptional gene regulation under chronic hypoxia in HCT116 cells.
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spelling doaj-art-fa29c5c95a2048d18e009927eb63017d2025-08-20T02:27:53ZengNature PortfolioScientific Reports2045-23222025-04-0115112010.1038/s41598-025-91828-wFragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cellsYoko Ogura0Xiaoning Sun1Zaijun Zhang2Kentaro Kawata3Jinyu Wu4Ryuma Matsubara5Atsuko Nakanishi Ozeki6Kenzui Taniue7Rena Onoguchi-Mizutani8Shungo Adachi9Koh Nakayama10Nobuhito Goda11Nobuyoshi Akimitsu12Department of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of TokyoAdvanced Interdisciplinary Studies, Engineering Department, The University of TokyoDepartment of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of TokyoIsotope Science Center, The University of TokyoDepartment of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of TokyoIsotope Science Center, The University of TokyoIsotope Science Center, The University of TokyoIsotope Science Center, The University of TokyoIsotope Science Center, The University of TokyoDepartment of Proteomics, National Cancer Center Research InstituteDepartment of Pharmacology, School of Medicine, Asahikawa Medical UniversityDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda UniversityIsotope Science Center, The University of TokyoAbstract Oxygen shortage, known as hypoxia, occurs commonly in both physiological and pathological conditions. Transcriptional regulation by hypoxia-inducible factors is a dominant regulatory mechanism controlling hypoxia-responsive genes during acute hypoxia; however, recent studies suggest that post-transcriptional regulation, including RNA degradation, also involves hypoxia-induced gene expression during the chronic hypoxia. In this study, we developed a method to quantify the contributions of RNA synthesis and degradation to differential gene expression, and identified 102 genes mainly regulated via RNA degradation under chronic hypoxia in HCT116 cells. Bioinformatics analysis showed that the genes mainly regulated by RNA degradation were involved in glycolysis. We examined changes in the RNA-binding ability of RNA-binding proteins by RNA interactome capture and statistical analysis using public databases. We identified fragile X messenger ribonucleoprotein 1 (FMRP) as an RNA-binding protein involved in the chronic hypoxia-induced increase in mRNAs encoding rate-limiting enzymes. This study emphasizes the importance of post-transcriptional gene regulation under chronic hypoxia in HCT116 cells.https://doi.org/10.1038/s41598-025-91828-wGlycolysisHypoxiaMetabolic labelingRNA degradationRNA synthesis
spellingShingle Yoko Ogura
Xiaoning Sun
Zaijun Zhang
Kentaro Kawata
Jinyu Wu
Ryuma Matsubara
Atsuko Nakanishi Ozeki
Kenzui Taniue
Rena Onoguchi-Mizutani
Shungo Adachi
Koh Nakayama
Nobuhito Goda
Nobuyoshi Akimitsu
Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells
Scientific Reports
Glycolysis
Hypoxia
Metabolic labeling
RNA degradation
RNA synthesis
title Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells
title_full Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells
title_fullStr Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells
title_full_unstemmed Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells
title_short Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells
title_sort fragile x messenger ribonucleoprotein 1 fmrp regulates glycolytic gene expression under chronic hypoxia in hct116 cells
topic Glycolysis
Hypoxia
Metabolic labeling
RNA degradation
RNA synthesis
url https://doi.org/10.1038/s41598-025-91828-w
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