Browsing by Author "Rossi, Annalisa"

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    Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS
    (Nature Publishing Group, 2020-09-21) 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; Medicine, School of Medicine
    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.