Intragenic alternative splicing coordination is essential for Caenorhabditis elegans slo-1 gene function
- Glauser, Dominique A. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, USA - Department of Biology/Zoology, University of Fribourg, 1700 Fribourg, Switzerland
- Johnson, Brandon E. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, USA
- Aldrich, Richard W. Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, USA
- Goodman, Miriam B. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, USA
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2011
Published in:
- Proceedings of the National Academy of Sciences. - 2011, vol. 108, no. 51, p. 20790-20795
English
Alternative splicing is critical for diversifying eukaryotic proteomes, but the rules governing and coordinating splicing events among multiple alternate splice sites within individual genes are not well understood. We developed a quantitative PCR-based strategy to quantify the expression of the 12 transcripts encoded by the Caenorhabditis elegans slo-1 gene, containing three alternate splice sites. Using conditional probability-based models, we show that splicing events are coordinated across these sites. Further, we identify a point mutation in an intron adjacent to one alternate splice site that disrupts alternative splicing at all three sites. This mutation leads to aberrant synaptic transmission at the neuromuscular junction. In a genomic survey, we found that a UAAAUC element disrupted by this mutation is enriched in introns flanking alternate exons in genes with multiple alternate splice sites. These results establish that proper coordination of intragenic alternative splicing is essential for normal physiology of slo-1 in vivo and identify putative specialized cis-regulatory elements that regulate the coordination of intragenic alternative splicing.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 28355
- DOI 10.1073/pnas.1116712108
- Persistent URL
- https://folia.unifr.ch/unifr/documents/302259
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