Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction
Summary: Glutamine:fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP). A 54-bp exon 9 of GFPT1 is specifically included in skeletal and cardiac muscles to generate a long isoform of GFPT1 (GFPT1-L). We showed that SRSF1 and Rbfox1/2 c...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223018230 |
| _version_ | 1827781734041649152 |
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| author | Paniz Farshadyeganeh Mohammad Nazim Ruchen Zhang Bisei Ohkawara Kazuki Nakajima Mohammad Alinoor Rahman Farhana Nasrin Mikako Ito Jun-ichi Takeda Kenji Ohe Yuki Miyasaka Tamio Ohno Akio Masuda Kinji Ohno |
| author_facet | Paniz Farshadyeganeh Mohammad Nazim Ruchen Zhang Bisei Ohkawara Kazuki Nakajima Mohammad Alinoor Rahman Farhana Nasrin Mikako Ito Jun-ichi Takeda Kenji Ohe Yuki Miyasaka Tamio Ohno Akio Masuda Kinji Ohno |
| author_sort | Paniz Farshadyeganeh |
| collection | DOAJ |
| description | Summary: Glutamine:fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP). A 54-bp exon 9 of GFPT1 is specifically included in skeletal and cardiac muscles to generate a long isoform of GFPT1 (GFPT1-L). We showed that SRSF1 and Rbfox1/2 cooperatively enhance, and hnRNP H/F suppresses, the inclusion of human GFPT1 exon 9 by modulating recruitment of U1 snRNP. Knockout (KO) of GFPT1-L in skeletal muscle markedly increased the amounts of GFPT1 and UDP-HexNAc, which subsequently suppressed the glycolytic pathway. Aged KO mice showed impaired insulin-mediated glucose uptake, as well as muscle weakness and fatigue likely due to abnormal formation and maintenance of the neuromuscular junction. Taken together, GFPT1-L is likely to be acquired in evolution in mammalian striated muscles to attenuate the HBP for efficient glycolytic energy production, insulin-mediated glucose uptake, and the formation and maintenance of the neuromuscular junction. |
| first_indexed | 2024-03-11T15:22:58Z |
| format | Article |
| id | doaj.art-3389bd93cb9e4caaa6d1fa76afe19c00 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:22:58Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3389bd93cb9e4caaa6d1fa76afe19c002023-10-28T05:08:16ZengElsevieriScience2589-00422023-10-012610107746Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junctionPaniz Farshadyeganeh0Mohammad Nazim1Ruchen Zhang2Bisei Ohkawara3Kazuki Nakajima4Mohammad Alinoor Rahman5Farhana Nasrin6Mikako Ito7Jun-ichi Takeda8Kenji Ohe9Yuki Miyasaka10Tamio Ohno11Akio Masuda12Kinji Ohno13Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USADivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanInstitute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, JapanDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Biochemistry and Molecular Biology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205, USADivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Biochemistry and Molecular Biology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205, USADivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, JapanDivision of Experimental Animals, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDivision of Experimental Animals, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Corresponding authorDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Corresponding authorSummary: Glutamine:fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP). A 54-bp exon 9 of GFPT1 is specifically included in skeletal and cardiac muscles to generate a long isoform of GFPT1 (GFPT1-L). We showed that SRSF1 and Rbfox1/2 cooperatively enhance, and hnRNP H/F suppresses, the inclusion of human GFPT1 exon 9 by modulating recruitment of U1 snRNP. Knockout (KO) of GFPT1-L in skeletal muscle markedly increased the amounts of GFPT1 and UDP-HexNAc, which subsequently suppressed the glycolytic pathway. Aged KO mice showed impaired insulin-mediated glucose uptake, as well as muscle weakness and fatigue likely due to abnormal formation and maintenance of the neuromuscular junction. Taken together, GFPT1-L is likely to be acquired in evolution in mammalian striated muscles to attenuate the HBP for efficient glycolytic energy production, insulin-mediated glucose uptake, and the formation and maintenance of the neuromuscular junction.http://www.sciencedirect.com/science/article/pii/S2589004223018230Biological sciencesBiochemistryPhysiology |
| spellingShingle | Paniz Farshadyeganeh Mohammad Nazim Ruchen Zhang Bisei Ohkawara Kazuki Nakajima Mohammad Alinoor Rahman Farhana Nasrin Mikako Ito Jun-ichi Takeda Kenji Ohe Yuki Miyasaka Tamio Ohno Akio Masuda Kinji Ohno Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction iScience Biological sciences Biochemistry Physiology |
| title | Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction |
| title_full | Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction |
| title_fullStr | Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction |
| title_full_unstemmed | Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction |
| title_short | Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction |
| title_sort | splicing regulation of gfpt1 muscle specific isoform and its roles in glucose metabolisms and neuromuscular junction |
| topic | Biological sciences Biochemistry Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223018230 |
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