Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing

Neurexins are presynaptic cell-adhesion molecules that are essential for synapse formation and synaptic transmission. Extensive alternative splicing of neurexin transcripts may generate thousands of isoforms, but it is unclear how many distinct neurexins are physiologically produced. We used unbiased long-read sequencing of full-length neurexin mRNAs to systematically assess the alternative splicing of neurexins in prefrontal cortex. We identified a novel, abundantly used alternatively spliced exon of neurexins, and found that the different events of alternative splicing of neurexins appear to be independent of each other. Our data suggest that thousands of neurexin isoforms are physiologically generated, consistent with the notion that neurexins represent transsynaptic protein-interaction scaffolds that mediate diverse functions and are regulated by alternative splicing at multiple independent sites.