Structure of the mouse gonadotropin-releasing hormone receptor gene: variant transcripts generated by alternative...

Area of Science:

• Molecular Biology
• Genetics
• Endocrinology

Background:

• The mouse gonadotropin-releasing hormone receptor (GnRHR) is a G-protein-coupled receptor with a unique lack of a carboxy-terminal domain.
• Understanding GnRHR transcript variants is crucial for comprehending its function and regulation.

Purpose of the Study:

• To investigate the structural basis and origins of alternative GnRHR transcripts in mice.
• To elucidate the gene structure of the mouse GnRHR.

Main Methods:

• Screening of a gonadotrope cell line cDNA library to identify variant receptor transcripts.
• Mapping the mouse GnRHR gene structure using genomic clones.
• Southern blot analysis of mouse genomic DNA.
• Comparative analysis of cDNA and genomic sequences.

Main Results:

• The mouse GnRHR gene comprises three exons spanning over 22 kb.
• 42 variant cDNA clones were identified, with the majority (71%) encoding the functional 327-amino-acid receptor.
• Alternative processing resulted in variant transcripts encoding shorter proteins (261 and 177 amino acids) due to exon skipping or alternative polyadenylation.

Conclusions:

• The mouse GnRHR gene exhibits alternative processing, leading to diverse transcript variants.
• These findings explain the origin of previously identified variant cDNAs.
• Alternative splicing and polyadenylation are key mechanisms generating functional and non-functional GnRHR isoforms.