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Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS.
Wu, Xue; Niculite, Cristina M; Preda, Mihai Bogdan; Rossi, Annalisa; Tebaldi, Toma; Butoi, Elena; White, Mattie K; Tudoran, Oana M; Petrusca, Daniela N; Jannasch, Amber S; Bone, William P; Zong, Xingyue; Fang, Fang; Burlacu, Alexandrina; Paulsen, Michelle T; Hancock, Brad A; Sandusky, George E; Mitra, Sumegha; Fishel, Melissa L; Buechlein, Aaron; Ivan, Cristina; Oikonomopoulos, Spyros; Gorospe, Myriam; Mosley, Amber; Radovich, Milan; Davé, Utpal P; Ragoussis, Jiannis; Nephew, Kenneth P; Mari, Bernard; McIntyre, Alan; Konig, Heiko; Ljungman, Mats; Cousminer, Diana L; Macchi, Paolo; Ivan, Mircea.
Affiliation
  • Wu X; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Niculite CM; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Preda MB; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Rossi A; "Victor Babes" National Institute of Pathology, Bucharest, Romania.
  • Tebaldi T; Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania.
  • Butoi E; Laboratory of Molecular and Cellular Neurobiology, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy.
  • White MK; Laboratory of Translational Genomics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy.
  • Tudoran OM; Yale Cancer Center, Yale University School of Medicine, New Haven, CT, 06520, USA.
  • Petrusca DN; Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania.
  • Jannasch AS; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Bone WP; The Oncology Institute "Prof Dr. Ion Chiricuta", Cluj-Napoca, Romania.
  • Zong X; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Fang F; Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN, 47907, USA.
  • Burlacu A; Department of Genetics, Department of Systems Pharmacology and Translational Therapeutics, Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Paulsen MT; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Hancock BA; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Sandusky GE; Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania.
  • Mitra S; Departments of Radiation Oncology and Environmental Health Sciences, Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Fishel ML; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Buechlein A; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Ivan C; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
  • Oikonomopoulos S; Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Gorospe M; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
  • Mosley A; Department of Pharmacology and Toxicology, Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Radovich M; Indiana University Center for Genomics and Bioinformatics, Bloomington, IN, 47405, USA.
  • Davé UP; Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Ragoussis J; Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, McGill University, Montréal, QC, Canada.
  • Nephew KP; Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Mari B; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • McIntyre A; Departments of Radiation Oncology and Environmental Health Sciences, Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Konig H; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
  • Ljungman M; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Cousminer DL; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Macchi P; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
  • Ivan M; Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, McGill University, Montréal, QC, Canada.
Nat Commun ; 11(1): 4755, 2020 09 21.
Article in En | MEDLINE | ID: mdl-32958772
ABSTRACT
We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxygen / Sterols / RNA, Long Noncoding / Homeostasis Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxygen / Sterols / RNA, Long Noncoding / Homeostasis Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: