Authors: Holter, Jethro¹; Davies, Jeffrey¹; Leresche, Nathalie²; Crunelli, Vincenzo¹; Carter, David³

Source: Journal of Molecular Neuroscience, Volume 26, Number 1, February 2005 , pp. 99-108(10)

Publisher: Humana Press

Abstract:

Inhibitory neurotransmission in the mammalian brain is principally mediated by γ-aminobutyric acid (GABA) acting through different subtypes of cell membrane GABA receptor (GABAR). The expression of one GABAR gene, GABABR1, is distinguished by the expression of multiple splice variants that encode different isoforms of the receptor. In the present study, we have identified two novel GABABR1 variants, GABABR1h (R1h) and GABABR1i (R1i), which appear to arise from alternative splicing of the GABABR1 gene. The expression of R1h and R1i is differentially regulated in brain and peripheral tissues, but expression is not altered in the brain of a genetic model of absence epilepsy (GAERS rat [genetic absence epilepsy rat from Strasbourg]). Both the R1h and R1i variants exhibit a novel 80-bp insert downstream of exon 4 that is flanked by consensus splice sites, and both encode C-terminal-truncated proteins. The new insight into the family of GABABR1 variants gained from this study identifies exon 4 as a preferred locus, or hot spot for regulated splicing in the GABABR1 gene. This finding correlates with the micro-exonic nature of exon 4 (21 bp). Bioinformatic analysis of micro-exon 4 and its flanking pre-mRNA sequences has revealed multiple, potentially competitive, exonic splicing enhancers that provide a mechanistic basis for the preponderance of alternative splicing events at this locus. Conservation of GABABR1 micro-exon 4 across species suggests a conserved functional role, facilitating either N-terminal protein production or post-transcriptional gene regulation through regulated splicing coupled to transcript decay.

Keywords: GABA; GABAB receptor; alternative splicing; micro-exon; absence epilepsy

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:26:1:099

Affiliations: 1: School of Biosciences, Cardiff University, Cardiff, UK, 2: Equipe Neurobiologie Cellulaire, UMR 7102, CNRS Université Paris VI, F-75005, Paris, France, 3: School of Biosciences, Cardiff University, Cardiff, UK, Email: smbdac@cardiff.ac.uk

Publication date: 2005-02-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Anatomy & Physiology ,  Zoology ,  Neurology & Psychiatry
• By this author: Holter, Jethro ;  Davies, Jeffrey ;  Leresche, Nathalie ;  Crunelli, Vincenzo ;  Carter, David

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers