Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity
Summary: The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) to measure the nascent transcriptional response to fasting and refeeding as well as define the specific role of...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222006812 |
| _version_ | 1818239152457515008 |
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| author | Dominic Santoleri Hee-Woong Lim Matthew J. Emmett Julian Stoute Matthew J. Gavin Jaimarie Sostre-Colón Kahealani Uehara Jaclyn E. Welles Kathy Fange Liu Mitchell A. Lazar Paul M. Titchenell |
| author_facet | Dominic Santoleri Hee-Woong Lim Matthew J. Emmett Julian Stoute Matthew J. Gavin Jaimarie Sostre-Colón Kahealani Uehara Jaclyn E. Welles Kathy Fange Liu Mitchell A. Lazar Paul M. Titchenell |
| author_sort | Dominic Santoleri |
| collection | DOAJ |
| description | Summary: The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) to measure the nascent transcriptional response to fasting and refeeding as well as define the specific role of hepatic Akt and FoxO1 signaling in mediating this response. We identified 599 feeding-regulated transcripts, as well as over 6,000 eRNAs, and mapped their dependency on Akt and FoxO1 signaling. Further, we identified several feeding-regulated lncRNAs, including the lncRNA Gm11967, whose expression was dependent upon the liver Akt-FoxO1 axis. Restoring Gm11967 expression in mice lacking liver Akt improved insulin sensitivity and induced glucokinase protein expression, indicating that Akt-dependent control of Gm11967 contributes to the translational control of glucokinase. More broadly, we have generated a unique genome-wide dataset that defines the feeding and Akt/FoxO1-dependent transcriptional changes in response to nutrient availability. |
| first_indexed | 2024-12-12T12:53:00Z |
| format | Article |
| id | doaj.art-7c71e331dbf74cd59745668fc81b8721 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T12:53:00Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-7c71e331dbf74cd59745668fc81b87212022-12-22T00:23:57ZengElsevieriScience2589-00422022-06-01256104410Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivityDominic Santoleri0Hee-Woong Lim1Matthew J. Emmett2Julian Stoute3Matthew J. Gavin4Jaimarie Sostre-Colón5Kahealani Uehara6Jaclyn E. Welles7Kathy Fange Liu8Mitchell A. Lazar9Paul M. Titchenell10Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Biomedical Graduate Studies, Philadelphia, PA 19104, USA; Institute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USADivision of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USADepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USABiochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Biomedical Graduate Studies, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USAInstitute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USAInstitute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USABiochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Biomedical Graduate Studies, Philadelphia, PA 19104, USA; Institute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USAInstitute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USABiochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Biomedical Graduate Studies, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USAInstitute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USABiochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Biomedical Graduate Studies, Philadelphia, PA 19104, USA; Institute of Diabetes, Obesity and Metabolism, Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA 19104, USA; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Corresponding authorSummary: The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) to measure the nascent transcriptional response to fasting and refeeding as well as define the specific role of hepatic Akt and FoxO1 signaling in mediating this response. We identified 599 feeding-regulated transcripts, as well as over 6,000 eRNAs, and mapped their dependency on Akt and FoxO1 signaling. Further, we identified several feeding-regulated lncRNAs, including the lncRNA Gm11967, whose expression was dependent upon the liver Akt-FoxO1 axis. Restoring Gm11967 expression in mice lacking liver Akt improved insulin sensitivity and induced glucokinase protein expression, indicating that Akt-dependent control of Gm11967 contributes to the translational control of glucokinase. More broadly, we have generated a unique genome-wide dataset that defines the feeding and Akt/FoxO1-dependent transcriptional changes in response to nutrient availability.http://www.sciencedirect.com/science/article/pii/S2589004222006812PhysiologyMolecular PhysiologyOmicsTranscriptomics |
| spellingShingle | Dominic Santoleri Hee-Woong Lim Matthew J. Emmett Julian Stoute Matthew J. Gavin Jaimarie Sostre-Colón Kahealani Uehara Jaclyn E. Welles Kathy Fange Liu Mitchell A. Lazar Paul M. Titchenell Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity iScience Physiology Molecular Physiology Omics Transcriptomics |
| title | Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity |
| title_full | Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity |
| title_fullStr | Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity |
| title_full_unstemmed | Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity |
| title_short | Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity |
| title_sort | global run on sequencing identifies gm11967 as an akt dependent long noncoding rna involved in insulin sensitivity |
| topic | Physiology Molecular Physiology Omics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222006812 |
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