Nova-1 mediates glucocorticoid-induced inhibition of Pre-mRNA splicing of gonadotropin-releasing hormone transcripts

Eonyoung Park, Mi Sun Lee, Sun Mi Baik, Eun Bee Cho, Gi Hoon Son, Jae Young Seong, Kun Ho Lee, Kyunglin Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish
Pages (from-to)12792-12800
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number19
DOIs
Publication statusPublished - 2009 May 8

Fingerprint

RNA Precursors
Gonadotropin-Releasing Hormone
Glucocorticoids
Introns
Antigens
Dexamethasone
Gene expression
Messenger RNA
Gene Expression
Hypothalamus
Exons
Brain
Down-Regulation

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 journalArticle

Park, Eonyoung ; Lee, Mi Sun ; Baik, Sun Mi ; Cho, Eun Bee ; Son, Gi Hoon ; Seong, Jae Young ; Lee, Kun Ho ; Kim, Kyunglin. / Nova-1 mediates glucocorticoid-induced inhibition of Pre-mRNA splicing of gonadotropin-releasing hormone transcripts. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 19. pp. 12792-12800.
@article{b296f082dd214c2fb88e863764cbd490,
title = "Nova-1 mediates glucocorticoid-induced inhibition of Pre-mRNA splicing of gonadotropin-releasing hormone transcripts",
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.",
author = "Eonyoung Park and Lee, {Mi Sun} and Baik, {Sun Mi} and Cho, {Eun Bee} and Son, {Gi Hoon} and Seong, {Jae Young} and Lee, {Kun Ho} and Kyunglin Kim",
year = "2009",
month = "5",
day = "8",
doi = "10.1074/jbc.M807386200",
language = "English",
volume = "284",
pages = "12792--12800",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "19",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=67649781703&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649781703&partnerID=8YFLogxK

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 -