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Role of the 5′ untranslated region (UTR) in the tissue‐specific regulation of rat tryptophan hydroxylase gene expression by stress
Author(s) -
Chamas Firas,
Sabban Esther L.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00989.x
Subject(s) - tryptophan hydroxylase , gene isoform , biology , messenger rna , brainstem , microbiology and biotechnology , gene expression , untranslated region , serotonergic , gene , serotonin , biochemistry , receptor , neuroscience
There are tissue specific discrepancies in expression of tryptophan hydroxylase (TPH) between the pineal gland and brainstem. TPH mRNA levels in the pineal are much higher than in the brainstem, however, the two tissues contain comparable protein levels. This discrepancy could result from different translation efficiency of two of the TPH mRNA isoforms. Using PCR‐based methods, we analyzed the relative expression, in pineal and brainstem, of two TPH mRNA isoforms differing in the length of their untranslated region (5′UTR). The levels of the TPHα were found to be 960‐fold more abundant than the 51‐nucleotide longer TPHβ, in the pineal. TPHβ was also detected for the first time in the brainstem, where TPHβ/TPHα was about five‐fold higher than in the pineal. To study the role of the different 5′UTRs, each was cloned in‐frame upstream of luciferase, and transfected into PC12 cells. Both 5′UTRs enhanced luciferase activity, with TPHβ 5′UTR being more effective than TPHα 5′UTR, indicating selective regulation of translation efficiency. We also examined whether physiological manipulations alter the distribution of the TPH mRNA isoforms. Repeated stress had no effect in pineal, but led to a marked preferential induction of TPHβ in brainstem. Modulation of TPH gene expression in serotonergic neurons could result from selective and tissue specific regulation of its mRNA isoforms.