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Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

Author

Listed:
  • Xue Wu

    (Indiana University School of Medicine
    Indiana University School of Medicine)

  • Cristina M. Niculite

    (Indiana University School of Medicine
    “Victor Babes” National Institute of Pathology)

  • Mihai Bogdan Preda

    (Institute of Cellular Biology and Pathology “Nicolae Simionescu”)

  • Annalisa Rossi

    (Computational and Integrative Biology - CIBIO, University of Trento)

  • Toma Tebaldi

    (Computational and Integrative Biology - CIBIO, University of Trento
    Yale University School of Medicine)

  • Elena Butoi

    (Institute of Cellular Biology and Pathology “Nicolae Simionescu”)

  • Mattie K. White

    (Indiana University School of Medicine)

  • Oana M. Tudoran

    (The Oncology Institute “Prof Dr. Ion Chiricuta”)

  • Daniela N. Petrusca

    (Indiana University School of Medicine)

  • Amber S. Jannasch

    (Purdue University)

  • William P. Bone

    (University of Pennsylvania)

  • Xingyue Zong

    (Indiana University School of Medicine)

  • Fang Fang

    (Indiana University School of Medicine)

  • Alexandrina Burlacu

    (Institute of Cellular Biology and Pathology “Nicolae Simionescu”)

  • Michelle T. Paulsen

    (Center for RNA Biomedicine, University of Michigan)

  • Brad A. Hancock

    (Indiana University School of Medicine)

  • George E. Sandusky

    (Indiana University School of Medicine)

  • Sumegha Mitra

    (Indiana University
    Indiana University School of Medicine)

  • Melissa L. Fishel

    (Indiana University
    Indiana University School of Medicine)

  • Aaron Buechlein

    (Indiana University Center for Genomics and Bioinformatics)

  • Cristina Ivan

    (The University of Texas MD Anderson Cancer Center)

  • Spyros Oikonomopoulos

    (Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, McGill University)

  • Myriam Gorospe

    (National Institutes of Health)

  • Amber Mosley

    (Indiana University School of Medicine)

  • Milan Radovich

    (Center for RNA Biomedicine, University of Michigan
    Indiana University)

  • Utpal P. Davé

    (Indiana University School of Medicine
    Indiana University School of Medicine
    Indiana University)

  • Jiannis Ragoussis

    (Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, McGill University)

  • Kenneth P. Nephew

    (Indiana University School of Medicine
    Indiana University
    Indiana University School of Medicine)

  • Bernard Mari

    (CNRS, IPMC, FHU-OncoAge, Université Côte d’Azur)

  • Alan McIntyre

    (University of Michigan)

  • Heiko Konig

    (Indiana University School of Medicine
    Indiana University)

  • Mats Ljungman

    (Center for RNA Biomedicine, University of Michigan
    Nottingham University)

  • Diana L. Cousminer

    (University of Pennsylvania)

  • Paolo Macchi

    (Computational and Integrative Biology - CIBIO, University of Trento)

  • Mircea Ivan

    (Indiana University School of Medicine
    Indiana University School of Medicine
    Indiana University)

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.

Suggested Citation

  • Xue Wu & Cristina M. Niculite & Mihai Bogdan Preda & Annalisa Rossi & Toma Tebaldi & Elena Butoi & Mattie K. White & Oana M. Tudoran & Daniela N. Petrusca & Amber S. Jannasch & William P. Bone & Xingy, 2020. "Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18411-x
    DOI: 10.1038/s41467-020-18411-x
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