Utilization of an intron located polyadenlyation site resulted in four novel glutamate decarboxylase transcripts

Abstract

Glutamate decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in central nervous system (CNS). Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 65 kDa (GAD65) and 67 kDa (GAD67). In the present study, four novel GAD67 transcripts produced by alternative splicing and polyadenlyation were cloned from rat testis. These novel GAD67 transcripts were widely expressed in non-neuronal tissues. During rat testis maturation, their expression level showed a time dependent change. These transcripts were predicted to synthesis of GAD proteins truncated of the binding site for pyridoxal phosphate, an essential cofactor, therefore cannot function as a decarboxylase. Thus, post-transcriptional processing mechanism as alternative splicing and polyadenlyation may play a crucial role in regulating rat GAD67 gene expression.

GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

“…It has now become clear that GABA signaling also exists in peripheral organs. The testes have well-described components of the GABA system, including the three types of GABA receptor, GABA synthetic enzymes (GAD65 and GAD67), and a GABA transporter (GAT-1) [10][11][12][13][14]. However, very little is known about the precise roles and underlying mechanisms of GABA signaling during spermatogenesis.…”

Novel Diabetes Autoantibodies and Prediction of Type 1 Diabetes

“…At present, the mechanisms responsible for the breakdown in tolerance to diabetes autoantigens remains unclear, although one plausible theory is that differential expression in the thymus could allow potentially pathogenic T cells to escape negative selection. Consistent with this hypothesis splice variants for all four major autoantigens insulin;3, IA-2;3, GAD65;2, and ZnT8;5 have been reported [19–21], although not all encode distinct proteins. The biological relevance of variations in the ratios of thymic versus β cell expression of T1D autoantigen splice forms is an area of active investigation.…”

Identification and expression analysis of a novel transcript of the human PRMT2 gene resulted from alternative polyadenylation in breast cancer

“…Alternative RNA splicing and polyadenylation of genes are sophisticated nuclear processes, which allows the diversification of the protein products of a single gene in terms not only of their structure, but also their function and/or cellular localization (Stamm et al, 2005;Liu et al, 2009). PRMTs play a role in the control of mRNA processing and maturation by modulating the activity of RNA-binding proteins.…”

“…Thus exon 7 is a composite exon (Edwalds-Gilbert et al, 1997). Alternative polyadenylation sites can lead to mRNAs with variable 3′-UTRs as well as distinct protein products Liu et al, 2009). However, it is not understood why transcription of the human PRMT2 gene utilizes multiple poly(A) signal sequences, and this might depend on different cellular and genetic contexts.…”