Do new non-coding RNAs control an epigenetic program of appetite control?

  • Falaleeva, Marina (PI)

Grants and Contracts Details


Obesity is a major cause for atherosclerotic disease leading to heart attack and stroke. Obesity affects over 35% of Americans causing more than 400,000 deaths per year. After weight loss, hormonal changes continue to signal 'hunger' to individuals. This causes most people to regain weight after a diet, representing a major problem in weight reduction. The Prader-Willi syndrome (PWS) is the most common genetic cause for obesity. It is caused by the loss of expression of non-coding, processed small nucleolar RNAs (psnoRNAs), HBII-52 and HBII-85. I found that HBII-52 and HBII-85 psnoRNAs regulate mainly genes involved in lipid metabolism. In contrast to "traditional" small nucleolar RNAs (snoRNAs), HBII-52 and HBII-85 RNAs do not form canonical small nucleolar ribonucleoprotein complexes (snoRNPs). My preliminary data suggest that stability ofHBII-52 and HBII-85 psnoRNAs are regulated and that their expression decreases after food withdrawal in mouse brain. Furthermore, I found direct binding of psnoRNAs to regulated genes and changes in associated Histone 3 K27 acetylation. I therefore hypothesize that psnoRNAs regulate a coordinated set of genes by setting epigenetic marks. As the regulated genes are involved in lipid metabolism, they could provide a memory of former nutritional states and explain weight regain after the diet. I expect to unveil a new program of gene regulation that prevents permanent weight loss after a diet, which could be a significant advance in fighting obesity. The grant will allow me to work in interdisciplinary environment and expand my existing knowledge of RNA biology into lipidomics and chromatin regulation, which will give me a unique skill set for my future career.
Effective start/end date7/1/136/30/15


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