Alternative splicing across the C. elegans nervous system

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 neu...

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Main Authors: Alexis Weinreb, Erdem Varol, Alec Barrett, Rebecca M. McWhirter, Seth R. Taylor, Isabel Courtney, Manasa Basavaraju, Abigail Poff, John A. Tipps, Becca Collings, The CeNGEN Consortium, Smita Krishnaswamy, David M. Miller, Marc Hammarlund
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58293-5
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author Alexis Weinreb
Erdem Varol
Alec Barrett
Rebecca M. McWhirter
Seth R. Taylor
Isabel Courtney
Manasa Basavaraju
Abigail Poff
John A. Tipps
Becca Collings
The CeNGEN Consortium
Smita Krishnaswamy
David M. Miller
Marc Hammarlund
author_facet Alexis Weinreb
Erdem Varol
Alec Barrett
Rebecca M. McWhirter
Seth R. Taylor
Isabel Courtney
Manasa Basavaraju
Abigail Poff
John A. Tipps
Becca Collings
The CeNGEN Consortium
Smita Krishnaswamy
David M. Miller
Marc Hammarlund
author_sort Alexis Weinreb
collection DOAJ
description 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.
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spelling doaj-art-8ff62b5727d24ebbaabed5513d22b5ad2025-08-20T02:25:16ZengNature PortfolioNature Communications2041-17232025-05-0116112110.1038/s41467-025-58293-5Alternative splicing across the C. elegans nervous systemAlexis Weinreb0Erdem Varol1Alec Barrett2Rebecca M. McWhirter3Seth R. Taylor4Isabel Courtney5Manasa Basavaraju6Abigail Poff7John A. Tipps8Becca Collings9The CeNGEN ConsortiumSmita Krishnaswamy10David M. Miller11Marc Hammarlund12Department of Genetics, Yale University School of MedicineTandon School of Engineering, New York UniversityDepartment of Genetics, Yale University School of MedicineDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Genetics, Yale University School of MedicineDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Genetics, Yale University School of MedicineDepartment of Cell and Developmental Biology, Vanderbilt UniversityDepartment of Genetics, Yale University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-58293-5
spellingShingle Alexis Weinreb
Erdem Varol
Alec Barrett
Rebecca M. McWhirter
Seth R. Taylor
Isabel Courtney
Manasa Basavaraju
Abigail Poff
John A. Tipps
Becca Collings
The CeNGEN Consortium
Smita Krishnaswamy
David M. Miller
Marc Hammarlund
Alternative splicing across the C. elegans nervous system
Nature Communications
title Alternative splicing across the C. elegans nervous system
title_full Alternative splicing across the C. elegans nervous system
title_fullStr Alternative splicing across the C. elegans nervous system
title_full_unstemmed Alternative splicing across the C. elegans nervous system
title_short Alternative splicing across the C. elegans nervous system
title_sort alternative splicing across the c elegans nervous system
url https://doi.org/10.1038/s41467-025-58293-5
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