Work

Intragenic alternative splicing coordination is essential for Caenorhabditis elegans slo-1 gene function

Year: 2011

Type: article

Abstract: 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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1116712108

Authors: Dominique A. Glauser, Brandon E. Johnson, Richard W. Aldrich, Miriam B. Goodman

Institutions: University of Fribourg, Stanford Medicine, Stanford University, The University of Texas at Austin

Language: English

Topic: RNA Research and Splicing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of Neurological Disorders and Stroke

Awards: Molecular Basis of Sensory Transduction in C. elegans, Temperature Sensation and Its Behavioral Consequences, G6284345678, G982560260