Regulatory sequences in the 3' Untranslated region of the human cGMP-Phosphodiesterase {beta}-Subunit gene.
 

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Regulatory sequences in the 3' Untranslated region of the human cGMP-Phosphodiesterase {beta}-Subunit gene.
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Regulatory sequences in the 3' Untranslated region of the human cGMP-Phosphodiesterase {beta}-Subunit gene.

Invest Ophthalmol Vis Sci. 2009 Feb 14;

Authors: Verardo M, Viczian A, Piri N, Akhmedov NB, Knox BE, Farber DB

PURPOSE: Rod cGMP-phosphodiesterase, a key enzyme in visual transduction, is important for retinal integrity and function. Mutations in the gene encoding its beta-subunit (PDEbeta) cause retinal degeneration in animals and humans. Here we tested the hypothesis that elements in the 3'UTR of the PDEbeta gene are involved in the regulation of PDEbeta expression. METHODS: Involvement of the 3' untranslated region (3'UTR) of PDEbeta mRNA in the regulation of PDEbeta expression was assessed by transfecting Y-79 retinoblastoma cells or the heads of Xenopus laevis tadpoles with constructs containing the SV40 or PDEbeta promoter, the luciferase cDNA and either the SV40 or PDEbeta 3'UTR (or fragments of its sequence). RESULTS: Compared to the SV40 3'UTR (used as control), the entire PDEbeta 3'UTR decreased reporter gene expression in Y-79 retinoblastoma cells as well as in SY5Y neuroblastoma and 293 human embryonic kidney cell lines. However, we observed that two 100 nt fragments from the PDEbeta 3'UTR increased while its non-canonical poly-adenylation signal abolished reporter gene expression both in Y-79 retinoblastoma cells and in ex vivo experiments using Xenopus tadpole heads. In particular, an 11 nt element (EURE) in one of the 100 nt fragments was responsible for up-regulation of luciferase expression. CONCLUSION: Our studies indicate that the 3'UTR of the PDEbeta mRNA is involved in the very complex regulation of this gene's expression in the retina. Moreover, they show that the PDEbeta poly-A signal has a dominant inhibitory effect over two other regions in the 3'UTR that stimulate gene expression.

PMID: 19218616 [PubMed - as supplied by publisher]