The loss of two regulatory RNAs is critical for the development of Prader-Willi syndrome. One of these RNAs prevents the formation of a truncated serotonin receptor. We will test the role of this truncated serotonin receptor in the production of growth hormones and determine whether it is a 'master regulator' for other receptors. Based on our preliminary studies and published literature, it is likely that the truncated receptor sequesters other receptors inside the cell, which prevents the production of growth hormone. This idea will be tested in cells and in mouse models. Importantly, we will determine weather a short synthetic RNA promotes growth hormone production and could substitute one of the missing regulatory RNAs.
The posterior pituitary expresses the serotonin receptor 2C. Welden JR, Zhang Z, Duncan MJ, Falaleeva M, Wells T, Stamm S. Neuroscience Letters. 2018 Jun 30.
The activity of the serotonin receptor 2C is regulated by alternative splicing. Stamm S, Gruber SB, Rabchevsky AG, Emeson RB. Human Genetics. 2017 Jun 29.
C/D-box snoRNAs form methylating and non-methylating ribonucleoprotein complexes: Old dogs show new tricks. Falaleeva M, Welden JR, Duncan MJ, Stamm S. 2017 Jun;39(6).
Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake. Zhang Z, Shen M, Gresch P, Ghamari-Langroudi M, Rabchevsky AG, Emeson R, Stamm S. EMBO Molecular Medicine, 2016 Aug; 8(8): 878–894.
Dual function of C/D box snoRNAs in rRNA modification and alternative pre-mRNA splicing. Falaleeva M, Pages A, Matuszek Z, Hidmi S, Agranat-Tamir L, Korotkov K, Nevo Y, Eyras E, Sperling R, Stamm S. Proceedings of the National Academy of Sciences of the United States of America, 2016 Mar 22;113(12):E1625-34.
SNORD116 and SNORD115 change expression of multiple genes and modify each other's activity. Falaleeva M, Surface J, Shen M, de la Grange P, Stamm S. Gene, 2015 Nov 10;572(2):266-73.
Stefan Stamm, PhD
University of Kentucky