Document Type

Article

Publication Date

11-4-2024

Keywords

JGM

JAX Source

NPJ Genom Med. 2024;9(1):54. Epub 20241104

ISSN

2056-7944

PMID

39496626

DOI

https://doi.org/10.1038/s41525-024-00432-w

Grant

This work was supported by National Institutes of Health grants R01CA248317 and R01GM138541 to OA. We acknowledge the use of shared resources supported by the JAX Cancer Center (National Cancer Institute P30CA034196). Funding for open access charge: JAX Institutional funding

Abstract

Numerous factors regulate alternative splicing of human genes at a co-transcriptional level. However, how alternative splicing depends on the regulation of gene expression is poorly understood. We leveraged data from the Genotype-Tissue Expression (GTEx) project to show a significant association of gene expression and splicing for 6874 (4.9%) of 141,043 exons in 1106 (13.3%) of 8314 genes with substantially variable expression in nine GTEx tissues. About half of these exons demonstrate higher inclusion with higher gene expression, and half demonstrate higher exclusion, with the observed direction of coupling being highly consistent across different tissues and in external datasets. The exons differ with respect to multiple characteristics and are enriched for hundreds of isoform-specific Gene Ontology annotations suggesting an important regulatory mechanism. Notably, splicing-expression coupling of exons with roles in JUN and MAP kinase signalling could play an important role during cell division.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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