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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,1,21]]},"abstract":"<jats:p>\n                    Loss of the tumor suppressor tuberous sclerosis complex 1 (\n                    <jats:italic>Tsc1<\/jats:italic>\n                    ) in the liver promotes gluconeogenesis and glucose intolerance. We asked whether this could be attributed to aberrant expression of small RNAs. We performed small-RNA sequencing on liver of\n                    <jats:italic>Tsc1<\/jats:italic>\n                    -knockout mice, and found that miRNAs of the delta-like homolog 1 (\n                    <jats:italic>Dlk1<\/jats:italic>\n                    )\u2013deiodinase iodothyronine type III (\n                    <jats:italic>Dio3<\/jats:italic>\n                    ) locus are up-regulated in an mTORC1-dependent manner. Sustained mTORC1 signaling during development prevented CpG methylation and silencing of the\n                    <jats:italic>Dlk1-Dio3<\/jats:italic>\n                    locus, thereby increasing miRNA transcription. Deletion of miRNAs encoded by the\n                    <jats:italic>Dlk1-Dio3<\/jats:italic>\n                    locus reduced gluconeogenesis, glucose intolerance, and fasting blood glucose levels. Thus, miRNAs contribute to the metabolic effects observed upon loss of TSC1 and hyperactivation of mTORC1 in the liver. Furthermore, we show that miRNA is a downstream effector of hyperactive mTORC1 signaling.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1918931117","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T20:10:02Z","timestamp":1578600602000},"page":"1524-1532","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Loss of TSC complex enhances gluconeogenesis via upregulation of\n                    <i>Dlk1-Dio3<\/i>\n                    locus miRNAs"],"prefix":"10.1073","volume":"117","author":[{"given":"Dritan","family":"Liko","sequence":"first","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Rzepiela","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel and Swiss Institute of Bioinformatics, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Vukojevic","sequence":"additional","affiliation":[{"name":"Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland;"},{"name":"Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, CH-4055 Basel, Switzerland;"},{"name":"Department Biozentrum, Life Sciences Training Facility, University of Basel, CH-4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Zavolan","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel and Swiss Institute of Bioinformatics, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Hall","sequence":"additional","affiliation":[{"name":"Biozentrum, University of Basel, CH-4056 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,1,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante M.","year":"2012","unstructured":"M. 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