title: A Long Non-coding RNA, lncLGR, Regulates Hepatic Glucokinase Expression and Glycogen Storage during Fasting.
abstract: Glucose levels in mammals are tightly controlled through multiple mechanisms to meet systemic energy demands. Downregulation of hepatic glucokinase (GCK) during fasting facilitates the transition of the liver from a glucose-consuming to a gluconeogenic organ. Here, we report the transcriptional regulation of hepatic GCK by a long non-coding RNA (lncRNA) named liver GCK repressor (lncLGR). lncLGR is induced by fasting, and physiological overexpression of lncLGR to mimic fasting levels effectively suppresses GCK expression and reduces hepatic glycogen content in mice. Consistently, lncLGR knockdown enhances GCK expression and glycogen storage in fasted mice. Mechanistically, lncLGR specifically binds to heterogenous nuclear ribonucleoprotein L (hnRNPL), which is further confirmed to be a transcriptional repressor of GCK in vivo. Finally, we demonstrate that lncLGR facilitates the recruitment of hnRNPL to the GCK promoter and suppresses GCK transcription. Our data establish a lncRNA-mediated mechanism that regulates hepatic GCK expression and glycogen deposition in a physiological context.
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Ruan
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cangelosi
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA. Electronic address: haiming.cao@nih.gov.
authors.forename: Haiming
authors.initials: H
authors.lastname: Cao
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D005215:Fasting; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D005941:Glucokinase / Q000235:genetics* / Q000378:metabolism; D005943:Gluconeogenesis / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis* / Q000235:genetics; D006019:Glycolysis / Q000235:genetics*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014161:Transduction, Genetic
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007328:Insulin; D062085:RNA, Long Noncoding; C534662:hnRNPLL protein, mouse; D006003:Glycogen; D005941:Glucokinase; D005947:Glucose