Neuronal splicing, RNA binding proteins, and beyond the infinite

Summary

Date: 
January 28, 2020 - 12:00pm
Location: 
Bio Labs 1080
About the Speaker
Name: 
John Calarco
Speaker Title: 
Assistant Professor
Speaker Affiliation: 
University of Toronto

Nervous systems are composed of multiple neuronal subtypes, each with unique functional roles that collectively regulate the response to stimuli and behaviour. The terminal fates of these neuronal subtypes are thought to be programmed by transcription factors. However, post-transcriptional layers of gene regulation, such as alternative splicing, are being increasingly appreciated for their role in shaping the physiology of individual neuron types. In this seminar, I will highlight our efforts to characterize the repertoire of tissue and neuron-subtype specific splice variants in the model organism C. elegans using the Translating Ribosome Affinity Purification (TRAP-Seq) approach. Collectively, we have identified hundreds of isoforms that exhibit distinct splicing patterns across broad tissue types, and between neuronal subtypes. Intriguingly, our analysis has also identified examples of highly conserved micro-exons (<27 nucleotides), initially thought to exist primarily in vertebrate genomes. In a second project, I will describe our ongoing aim to map the expression and sub-cellular localization patterns of all neuronal RNA binding proteins at single neuron resolution in C. elegans, and insights we have discovered thus far. Collectively, we hope this work will provide a deeper understanding of the importance and mechanisms governing post-transcriptional gene regulation in the nervous system.