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| Status |
Public on Feb 24, 2021 |
| Title |
Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Examination of primary transcript level using the nascent RNA Bru-seq method, in MCF-7 cells cultured under normoxia (21% O2) or hypoxia (1% O2).
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| Contributor(s) |
Wu X, Niculite CM, Preda MB, Rossi A, Tebaldi T, Butoi E, White MK, Tudoran OM, Petrusca DN, Jannasch AS, Bone WP, Zong X, Fang F, Burlacu A, Paulsen MT, Hancock BA, Sandusky GE, Mitra S, Fishel ML, Buechlein A, Ivan C, Oikonomopoulos S, Gorospe0 M, Mosley A, Radovich M, Davé UP, Ragoussis J, Nephew KP, Mari B, McIntyre A, Konig H, Ljungman M, Cousminer DL, Macchi P, Ivan M |
| Citation(s) |
32958772 |
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| Submission date |
Jun 18, 2020 |
| Last update date |
Feb 27, 2021 |
| Contact name |
Mats Ljungman |
| E-mail(s) |
tenbroek@med.umich.edu, bedik@umich.edu, ivenkat@umich.edu
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| Organization name |
University of Michigan
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| Street address |
NCRC, B520 Room 1346 2800 Plymouth Rd.
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| City |
Ann Arbor |
| State/province |
Michigan |
| ZIP/Postal code |
48109-2800 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA640425 |
| SRA |
SRP267897 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE152799_RAW.tar |
5.1 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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