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 journalArticlepeer-review

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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