Wolfson Institute for Biomedical Research



WIBR Seminar

'Alternative splicing and RNA editing diversify CaV1.3 channel function in the brain'

Professor Tuck Soong Wah

Department of Medicine, National University of Singapore  

Host: Professor John Wood

Posttranscriptional mechanisms such as alternative splicing and RNA editing are exquisite means to fine-tune Ca2+-dependent regulation of voltage-gated (CaV) calcium channels. The generation of alternatively spliced isoforms and edited channels not only diversify function but it also influences the pharmacology of the channels.

Post-transcriptional modifications of the IQ-domain, encoded by exon 41, of the Cav1.3 L-type channels regulate Ca2+-dependent inhibition (CDI). The lack of CDI in the Cav1.3 channels may play an important role in cochlear amplification, neurotransmitter release and activity-dependent transcription in the hair cells or in the pacemaker activity of the suprachiasmatic neurons. We have recently discovered RNA editing at the IQ-domain resulting in the reduction of CDI. This pin-point modification is mediated by adenosine deaminase acting on RNA 2 (ADAR2) enzyme. ECS-/- mice genetically targeted to produce unedited CaV1.3 channels exhibited lower action potential spike frequencies in electrophysiological slice recordings of spontaneous oscillations in the suprachiasmatic neurons. These mice were shown to be more anxious, have better ability in spatial learning and have altered sleep patterns.

Overall, alternative splicing and RNA editing mechanisms contribute significantly to Ca2+ homeostasis via regulating Ca2+-dependent inhibition (CDI), a negative feedback mechanism on CaV1.3 channel function. 

Date: Thursday 9th February 2017 
Time: 4pm (please arrive 15 mins before start) 
Venue: Cruciform Café, 1st Floor Cruciform Building, Gower Street, UCL, WC1E 6BT
Refreshments will be provided