Cell differentiation of gonadotropin-releasing hormone neurons and alternative RNA splicing of the gonadotropin-releasing hormone transcript

Youngshik Choe, Gi Hoon Son, Sukwon Lee, Eonyoung Park, Younghye Moon, Kyungjin Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Two different, yet related issues regarding gonadotropin-releasing hormone (GnRH), i.e. the development and differentiation of hypothalamic GnRH neurons and the alternative RNA splicing of GnRH gene transcripts, are addressed in the present review. Using the immortalized GnRH-producing GT1 cell line, we found that activation of protein kinase C (PKC) with 12-O-tetradecanoylphorbol-13-acetate induces morphological and functional differentiation of these neurons. Specific isoforms of PKC are involved in neurite growth, cell migration and synaptic contacts and involve different signaling pathways. Using an in vitro splicing assay with HeLa nuclear extract, we found that excision of the first intron of the GnRH primary transcript is attenuated in non-GnRH-producing cells, but not in GnRH-producing cells such as GT1. This attenuation was relieved by exonic splicing enhancers located in the GnRH exons 3 and 4. Interestingly, addition of nuclear extract derived from GT1 cells further increased the excision rate of intron A, indicating that GnRH neurons contain trans-acting splicing factors. Extensive biochemical analysis indicates that Tra2α, a serine/arginine-rich RNA-binding protein, and other cofactors are likely involved in mediating neuron-specific excision of intron A from the GnRH primary transcript. An understanding of the GnRH neuron-specific splicing machinery provides critical insight into the molecular mechanism of GnRH gene regulation and consequently of mammalian reproductive development.

Original languageEnglish
Pages (from-to)282-290
Number of pages9
JournalNeuroendocrinology
Volume77
Issue number4
DOIs
Publication statusPublished - 2003 Jun 16
Externally publishedYes

    Fingerprint

Keywords

  • Cell migration
  • Exonic splicing enhancer
  • Gonadotropin-releasing hormone
  • Neurite outgrowth
  • Protein kinases
  • RNA binding proteins

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this