Research findings from Seoul National University update understanding of gene therapy
2009 JUL 9 - (NewsRx.com) -- "Glucocorticoid (GC) is known to affect the reproductive system by suppressing the gonadotropin-releasing hormone (GnRH) gene expression in the hypothalamus. However, the mechanism of this effect is poorly understood," scientists in Seoul, South Korea report. "We show here that the GC-induced reduction of GnRH mRNA is due to attenuation of a post-transcriptional process i.e. splicing of intron A. Treatment of dexamethasone (DEX), a synthetic GC, lowered GnRH mRNA transcripts and was accompanied by reduced excision of the first intron (intron A) from the GnRH pre-mRNA both in vitro and in vivo. While seeking to identify the splicing factors involved in GC-inhibited GnRH pre-mRNA splicing, we found that DEX down-regulated neuro-oncological ventral antigen-1 (Nova-1) mRNA and protein and that knockdown of Nova-1 reduced intron A excision from GnRH pre-mRNA. Nova-1 overexpression reversed the DEX-induced reduction of intron A excision. Nova-1 appears to promote intron A excision by binding to the distal region of exon 1 of the GnRH pre-mRNA," wrote E. Park and colleagues, Seoul National University. The researchers concluded: "Taken together, our findings indicate that the intron A excision by Nova-1 is a target of GC for down-regulation of GnRH gene expression, and more importantly, we characterized Nova-1, a brain-enriched splicing regulator responsible for GnRH pre-mRNA splicing.." Park and colleagues published their study in the Journal of Biological Chemistry (Nova-1 Mediates Glucocorticoid-induced Inhibition of Pre-mRNA Splicing of Gonadotropin-releasing Hormone Transcripts. Journal of Biological Chemistry, 2009;284(19):12792-12800). For additional information, contact K. Kim, Seoul National University, School Biology Science, Seoul 151742, South Korea. The publisher's contact information for the Journal of Biological Chemistry is: American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. Keywords: South Korea, Seoul, Biological Chemistry, Biotechnology, Dexamethasone, Drugs, Gene Therapy, Gonadotropin, Hormones, Interferon Alfa-2b, Intron, Intron A, Pharmaceuticals, Treatment, Seoul National University. This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2009, Gene Therapy Weekly via NewsRx.com.
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