THE ROLE OF 5'-UNTRANSLATED REGION OF THE HUMAN TRYPTOPHAN HYDROXYLASE 2 IN THE REGULATION OF GENE EXPRESSION IN DIFFERENT CELL LINES

Abstract

Dysregulation of brain serotonin levels has been implicated the causes of depressive disorders and serotonergic system is a common target for treatment. Tryptophan hydroxylase 2 is the neuro-specific rate-limiting enzyme in serotonin synthesis and by investigating the fundamental mechanisms of TPH2 regulation, further insights on the treatment of depressive disorders could be identified. In this study, five prime untranslated regions (5?UTR) of TPH2 was found to cause contrasting effects on TPH2 expression in HEK and PC12 cells tested by way of quantitative PCR, bioluminescence assay and doxycycline- inducible expression system. The results showed that 5?UTR causes an upregulation of the TPH2 mRNA and protein level only in PC12 cells. Further studies to determine potential factors involved in the 5?UTR upregulating effect are necessary to better understand the unique role of 5?UTR in gene regulation, which could in turn be used to target TPH2 activity for treatment of depressive disorders.