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LincNORS: A Noncoding Regulator of the Cellular Sterol Homeostasis II

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 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153292 | GEO | 2020/06/26

REPOSITORIES: GEO

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lincNORS: A Noncoding Regulator of the Cellular Sterol Homeostasis I

Project 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 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 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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The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

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