The serotonin receptor 2C (HTR2C) gene encodes a G protein-coupled receptor that is exclusively expressed in neurons. Here, we report that the 5' untranslated region of the receptor pre-mRNA as well as its hosted miRNAs is widely expressed in non-neuronal cell lines. Alternative splicing of HTR2C is regulated by MBII-52. MBII-52 and the neighboring MBII-85 cluster are absent in people with Prader-Willi syndrome, which likely causes the disease. We show that MBII-52 and MBII-85 increase expression of the HTR2C 5' UTR and influence expression of the hosted miRNAs. The data indicate that the transcriptional unit expressing HTR2C is more complex than previously recognized and likely deregulated in Prader-Willi syndrome.

This work was supported by NIH RO1 GM083187, P20RR020171 to SS; GM079549 to RS and JS; Binational Science Foundation (BSF), USA-Israel, transformative Grant, #2010508, to SS and RS. EE and AP were supported by the Spanish Ministry of Science with grant BIO2011-23920 and by Sandra Ibarra Foundation for Cancer with grant FSI 2011-035