Alternative splicing across the C. elegans nervous system
Alexis Weinreb, Erdem Varol, Alec Barrett, Rebecca M. McWhirter, Seth R. Taylor, Isabel Courtney, Manasa Basavaraju, Abigail Poff, John A. Tipps, Becca Collings, Cyril Cros, Berta Vidal, Maryam Majeed, Chen Wang, Emily A. Bayer, Molly Reilly, Eviatar Yemini, HaoSheng Sun, Oliver Hobert, Smita Krishnaswamy, David M. Miller, Marc Hammarlund
Abstract
Alternative splicing is a key mechanism that shapes transcriptomes, helping to define neuronal identity and modulate function. Here, we present an atlas of alternative splicing across the nervous system of Caenorhabditis elegans. Our analysis identifies novel alternative splicing in key neuronal genes such as unc-40/DCC and sax-3/ROBO. Globally, we delineate patterns of differential alternative splicing in almost 2000 genes, and estimate that a quarter of neuronal genes undergo differential splicing. We introduce a web interface for examination of splicing patterns across neuron types. We explore the relationship between neuron type and splicing, and between splicing and differential gene expression. We identify RNA features that correlate with differential alternative splicing and describe the enrichment of microexons. Finally, we compute a splicing regulatory network that can be used to generate hypotheses on the regulation and targets of alternative splicing in neurons. By affecting which form of a gene is expressed, alternative splicing is a major source of diversity in the nervous system. Here, the authors present an atlas of splice variants across neurons, and explore its impacts and mechanisms in the nematode nervous system.