Alternative splicing is coupled to gene expression in a subset of variably expressed genes.

IF 4.7 2区 医学 Q1 GENETICS & HEREDITY NPJ Genomic Medicine Pub Date : 2024-11-04 DOI:10.1038/s41525-024-00432-w
Guy Karlebach, Robin Steinhaus, Daniel Danis, Maeva Devoucoux, Olga Anczuków, Gloria Sheynkman, Dominik Seelow, Peter N Robinson
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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.

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在表达可变的基因子集中,替代剪接与基因表达相关联。
许多因素在共转录水平上调节人类基因的替代剪接。然而,人们对替代剪接如何依赖于基因表达调控还知之甚少。我们利用基因型-组织表达(GTEx)项目的数据显示,在 9 个 GTEx 组织中,8314 个基因中有 1106 个基因(13.3%)的 141043 个外显子中有 6874 个外显子(4.9%)的基因表达与剪接有显著关联,而这些基因的表达有很大差异。这些外显子中约有一半表现出较高的基因表达包容性,一半表现出较高的排斥性,在不同组织和外部数据集中观察到的耦合方向高度一致。这些外显子在多个特征方面存在差异,并富含数百个特异性同工酶基因本体注释,这表明存在一种重要的调控机制。值得注意的是,具有 JUN 和 MAP 激酶信号作用的外显子的剪接-表达耦合可能在细胞分裂过程中发挥重要作用。
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来源期刊
NPJ Genomic Medicine
NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
1.90%
发文量
67
审稿时长
17 weeks
期刊介绍: npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.
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