Spatiotemporal isoform profiling identifies a central activator of microexon splicing in C. elegans
- 1Department of Cell and Systems Biology, University of Toronto
Abstract
Dynamic alternative splicing programs drive tissue specification and organismal development. Here, we present the most comprehensive, tissue-resolved alternative splicing dataset in Caenorhabditis elegans to date, spanning three major tissue types from early embryogenesis to adulthood. We uncovered broad developmental and tissue-regulated alternative splicing trends and identified putative RNA-binding proteins (RBPs) coordinating co-regulated splicing networks governing tissue identity. Among the network of regulated splice variants, we uncovered additional, unannotated microexons for further study in C. elegans. Through a forward genetic screen, we identified RBM-25, a U1 snRNP-associated regulatory protein, as a key regulator that preferentially enhances the inclusion of short exons and microexons alongside its binding partner PRP-40. Phenotypic profiling of rbm-25 mutants demonstrated significant defects in behviour, reproductive fitness, lifespan, and synaptic signalling, indicating a key role for RBM-25-regulated target transcripts in normal physiology and behaviour. Together, these findings expand our appreciation for spatiotemporal isoform diversity during animal development, and provide mechanistic insights into how microexon splicing is regulated.
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BibTeX
@misc{koterniak2026spatiotemporal,
title = {{Spatiotemporal isoform profiling identifies a central activator of microexon splicing in C. elegans}},
author = {B. Koterniak and E. Liang and M. Zoberman and C. He and B. Choudhary and N. H. Sadek and P. P. Pilaka-Akella and A. D. Norris and J. A. Calarco},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751627},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751627v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Spatiotemporal isoform profiling identifies a central activator of microexon splicing in C. elegans
AU - B. Koterniak
AU - E. Liang
AU - M. Zoberman
AU - C. He
AU - B. Choudhary
AU - N. H. Sadek
AU - P. P. Pilaka-Akella
AU - A. D. Norris
AU - J. A. Calarco
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751627
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751627v1
AB - Dynamic alternative splicing programs drive tissue specification and organismal development. Here, we present the most comprehensive, tissue-resolved alternative splicing dataset in Caenorhabditis elegans to date, spanning three major tissue types from early embryogenesis to adulthood. We uncovered broad developmental and tissue-regulated alternative splicing trends and identified putative RNA-binding proteins (RBPs) coordinating co-regulated splicing networks governing tissue identity. Among the network of regulated splice variants, we uncovered additional, unannotated microexons for further study in C. elegans. Through a forward genetic screen, we identified RBM-25, a U1 snRNP-associated regulatory protein, as a key regulator that preferentially enhances the inclusion of short exons and microexons alongside its binding partner PRP-40. Phenotypic profiling of rbm-25 mutants demonstrated significant defects in behviour, reproductive fitness, lifespan, and synaptic signalling, indicating a key role for RBM-25-regulated target transcripts in normal physiology and behaviour. Together, these findings expand our appreciation for spatiotemporal isoform diversity during animal development, and provide mechanistic insights into how microexon splicing is regulated.
ER -