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, Smita Krishnaswamy (), David M. Miller () and Marc Hammarlund ()
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Alexis Weinreb: Yale University School of Medicine
Erdem Varol: New York University
Alec Barrett: Yale University School of Medicine
Rebecca M. McWhirter: Vanderbilt University
Seth R. Taylor: Vanderbilt University
Isabel Courtney: Vanderbilt University
Manasa Basavaraju: Yale University School of Medicine
Abigail Poff: Vanderbilt University
John A. Tipps: Vanderbilt University
Becca Collings: Vanderbilt University
Smita Krishnaswamy: Yale University School of Medicine
David M. Miller: Vanderbilt University
Marc Hammarlund: Yale University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58293-5

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