Abstract
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. 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. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 12792-12800 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 284 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 2009 May 8 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Nova-1 mediates glucocorticoid-induced inhibition of Pre-mRNA splicing of gonadotropin-releasing hormone transcripts. / Park, Eonyoung; Lee, Mi Sun; Baik, Sun Mi; Cho, Eun Bee; Son, Gi Hoon; Seong, Jae Young; Lee, Kun Ho; Kim, Kyunglin.
In: Journal of Biological Chemistry, Vol. 284, No. 19, 08.05.2009, p. 12792-12800.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nova-1 mediates glucocorticoid-induced inhibition of Pre-mRNA splicing of gonadotropin-releasing hormone transcripts
AU - Park, Eonyoung
AU - Lee, Mi Sun
AU - Baik, Sun Mi
AU - Cho, Eun Bee
AU - Son, Gi Hoon
AU - Seong, Jae Young
AU - Lee, Kun Ho
AU - Kim, Kyunglin
PY - 2009/5/8
Y1 - 2009/5/8
N2 - 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. 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. 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.
AB - 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. 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. 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.
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U2 - 10.1074/jbc.M807386200
DO - 10.1074/jbc.M807386200
M3 - Article
C2 - 19282286
AN - SCOPUS:67649781703
VL - 284
SP - 12792
EP - 12800
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 19
ER -