Karlebach Guy, Steinhaus Robin, Danis Daniel, Devoucoux Maeva, Anczuków Olga, Sheynkman Gloria, Seelow Dominik, Robinson Peter N
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
NPJ Genom Med. 2024 Nov 4;9(1):54. doi: 10.1038/s41525-024-00432-w.
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.
众多因素在共转录水平上调节人类基因的可变剪接。然而，可变剪接如何依赖于基因表达的调控却知之甚少。我们利用基因型-组织表达（GTEx）项目的数据，发现在9个GTEx组织中表达有显著差异的8314个基因的141,043个外显子中，有6874个（4.9%）外显子的基因表达与剪接存在显著关联。这些外显子中约一半随着基因表达升高而内含率增加，另一半则随着基因表达升高而排除率增加，观察到的这种关联方向在不同组织和外部数据集中高度一致。这些外显子在多个特征方面存在差异，并且富含数百种异构体特异性的基因本体注释，提示存在一种重要的调控机制。值得注意的是，在JUN和丝裂原活化蛋白激酶信号传导中起作用的外显子的剪接-表达偶联可能在细胞分裂过程中发挥重要作用。
