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

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 O(2) in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subje...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505984/
https://www.ncbi.nlm.nih.gov/pubmed/32958772
http://dx.doi.org/10.1038/s41467-020-18411-x
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author 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
author_facet 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
author_sort Wu, Xue
collection PubMed
description 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 O(2) 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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spelling pubmed-75059842020-10-05 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 Nat Commun Article 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 O(2) 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. Nature Publishing Group UK 2020-09-21 /pmc/articles/PMC7505984/ /pubmed/32958772 http://dx.doi.org/10.1038/s41467-020-18411-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
title Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
title_full Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
title_fullStr Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
title_full_unstemmed Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
title_short Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
title_sort regulation of cellular sterol homeostasis by the oxygen responsive noncoding rna lincnors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505984/
https://www.ncbi.nlm.nih.gov/pubmed/32958772
http://dx.doi.org/10.1038/s41467-020-18411-x
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