ArticleNucleic acids research2021
Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- The RNA structural code: orchestrating gene expression and enabling precision therapies.Acta pharmacologica Sinica · 2026Review
- Regulatory paradigm of Dscam1 stochastic alternative splicing through conserved long-range RNA structures.Nucleic acids research · 2026Article
- Ancestral intronic splicing regulatory elements in the SCNbioRxiv : the preprint server for biology · 2026Article
- CAR-SPLASH identifies nascent pre-mRNA structures implicated in kinetic coupling and alternative splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The crosstalk between alternative splicing and circular RNA in cancer: pathogenic insights and therapeutic implications.Cellular & molecular biology letters · 2024Review
- Study of the RNA splicing kinetics via in vivo 5-EU labeling.RNA (New York, N.Y.) · 2024Article
- RNA structure in alternative splicing regulation: from mechanism to therapy.Acta biochimica et biophysica Sinica · 2024Review
- Article
- Causes, functions, and therapeutic possibilities of RNA secondary structure ensembles and alternative states.Cell chemical biology · 2024Review
- Pre-mRNA splicing and its cotranscriptional connections.Trends in genetics : TIG · 2023Review
- RNA in situ conformation sequencing reveals novel long-range RNA structures with impact on splicing.RNA (New York, N.Y.) · 2023Article
- RNA folding pathways from all-atom simulations with a variationally improved history-dependent bias.Biophysical journal · 2023Article
- A network of DZF proteins controls alternative splicing regulation and fidelity.Nucleic acids research · 2023Article
- How does precursor RNA structure influence RNA processing and gene expression?Bioscience reports · 2023Review
- Review
- Hidden RNA pairings counteract the "first-come, first-served" splicing principle to drive stochastic choice inScience advances · 2022Article
- Secondary structures in RNA synthesis, splicing and translation.Computational and structural biotechnology journal · 2022Review
- Article
- Conserved long-range base pairings are associated with pre-mRNA processing of human genes.Nature communications · 2021Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian Ate1 gene encodes an arginyl transferase enzyme with tumor suppressor function that depends on the inclusion of one of the two mutually exclusive exons (MXE), exons 7a and 7b. We report that the molecular mechanism underlying MXE splicing in Ate1 involves five conserved regulatory intronic elements R1-R5, of which R1 and R4 compete for base pairing with R3, while R2 and R5 form an ultra-long-range RNA structure spanning 30 Kb. In minigenes, single and double mutations that disrupt base pairings in R1R3 and R3R4 lead to the loss of MXE splicing, while compensatory triple mutations that restore RNA structure revert splicing to that of the wild type. In the endogenous Ate1 pre-mRNA, blocking the competing base pairings by LNA/DNA mixmers complementary to R3 leads to the loss of MXE splicing, while the disruption of R2R5 interaction changes the ratio of MXE. That is, Ate1 splicing is controlled by two independent, dynamically interacting, and functionally distinct RNA structure modules. Exon 7a becomes more included in response to RNA Pol II slowdown, however it fails to do so when the ultra-long-range R2R5 interaction is disrupted, indicating that exon 7a/7b ratio depends on co-transcriptional RNA folding. In sum, these results demonstrate that splicing is coordinated both in time and in space over very long distances, and that the interaction of these components is mediated by RNA structure.
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