ArticleBiophysical journal2020
Exon Definition Facilitates Reliable Control of Alternative Splicing in the RON Proto-Oncogene.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Coordinated alternative splicing decisions via stepwise exon definition.Nucleic acids research · 2026Article
- Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4.Nature structural & molecular biology · 2025Article
- Polymorphism of the prolactin gene and its association with reproductive traits in F2 local crossed chickens.Veterinary world · 2025Article
- Position-dependent effects of RNA-binding proteins in the context of co-transcriptional splicing.NPJ systems biology and applications · 2023Article
- High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance.Nature communications · 2022Article
- Splice site proximity influences alternative exon definition.RNA biology · 2022Article
- Dynamic mRNP Remodeling in Response to Internal and External Stimuli.Biomolecules · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing is a key step in eukaryotic gene expression that allows for the production of multiple transcript and protein isoforms from the same gene. Even though splicing is perturbed in many diseases, we currently lack insights into regulatory mechanisms promoting its precision and efficiency. We analyze high-throughput mutagenesis data obtained for an alternatively spliced exon in the proto-oncogene RON and determine the functional units that control this splicing event. Using mathematical modeling of distinct splicing mechanisms, we show that alternative splicing is based in RON on a so-called "exon definition" mechanism. Here, the recognition of the adjacent exons by the spliceosome is required for removal of an intron. We use our model to analyze the differences between the exon and intron definition scenarios and find that exon definition prevents the accumulation of deleterious, partially spliced retention products during alternative splicing regulation. Furthermore, it modularizes splicing control, as multiple regulatory inputs are integrated into a common net input, irrespective of the location and nature of the corresponding cis-regulatory elements in the pre-messenger RNA. Our analysis suggests that exon definition promotes robust and reliable splicing outcomes in RON splicing.
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Registered trials
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