ArticleGenes2026
Interdependent Regulation of Alternative Splicing by Serine/Arginine-Rich and Heterogeneous Nuclear Ribonucleoprotein Splicing Factors.
Article in Genes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The Co-Expression ofPlants (Basel, Switzerland) · 2026Article
- Novel LARS2 variants in patients with Perrault syndrome: expanding the genetic spectrum and phenotypic heterogeneity.Frontiers in genetics · 2026Article
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Funding
Abstract
backgroundAlternative pre-mRNA splicing is a combinatorial process involving serine/arginine-rich (SR) and heterogeneous nuclear ribonucleoprotein (hnRNP) splicing factors. These proteins can silence or enhance splicing based on their expression levels and binding positions.
objectivesTo better understand the combinatorial and interdependent regulation between SR and hnRNP splicing factors during alternative splicing.
methodsComputational analyses were performed using cell knockdown and binding datasets from available databases.
resultsAnalyses of differential splicing data for 9 SR proteins and 21 hnRNP knockdowns revealed statistically significant interdependent regulation among several RNA-binding protein (RBP) combinations, albeit at different levels. Neither SR proteins nor hnRNPs showed strong preferences for collaborating with specific RBP classes in mediating exon inclusion. While SRSF3, hnRNPK, hnRNPC, and hnRNPL stand out as major influencers of alternative splicing, they do so predominantly independent of other RBPs. Minor influencers of alternative splicing, such as hnRNPDL and hnRNPR, predominantly regulate exon inclusion in concert with other RBPs, indicating that exon inclusion can be mediated by both single and multiple RBPs. Interestingly, the higher the number of RBPs that regulate the inclusion of an exon, the more variable exon inclusion preferences become. Interdependently regulated exons are more modular and can be characterized by weaker splice sites compared to their independently regulated counterparts. A comparison of RBP interdependence between HeLa and other cell lines provides a framework that explains cell-type-specific alternative splicing.
conclusionsOur study highlights the importance of the interdependent regulation of alternative exons and identifies characteristics of interdependently regulated exons that differ from independently regulated exons.
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