ArticlePLoS genetics2021
A broad analysis of splicing regulation in yeast using a large library of synthetic introns.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- The power of many: when genetics met yeasts and high-throughput.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Intron location and sequence modulate gene expression in Yarrowia lipolytica.Nucleic acids research · 2026Article
- Article
- Splicing regulation and intron evolution in the short-intron ciliate model of endosymbiosis Paramecium bursaria.Nucleic acids research · 2026Article
- Control of gene output by intron RNA structure.bioRxiv : the preprint server for biology · 2025Article
- Conservation and Remodeling of Alternative Splicing Landscapes in the Evolution ofPlants (Basel, Switzerland) · 2025Article
- Predicting dynamic expression patterns in budding yeast with a fungal DNA language model.Research square · 2025Article
- Predicting dynamic expression patterns in budding yeast with a fungal DNA language model.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive analysis of Saccharomyces cerevisiae intron structures in vivo.Nature structural & molecular biology · 2025Article
- Autoregulation of RPL7B by inhibition of a structural splicing enhancer.Nucleic acids research · 2025Article
- Up-Frameshift Factors from Phytopathogenic Fungi Play a Crucial Role in Nonsense-Mediated mRNA Decay.Journal of fungi (Basel, Switzerland) · 2025Article
- DecodingbioRxiv : the preprint server for biology · 2025Article
- From benign to pathogenic variants and vice versa: pyrimidine transitions at position -3 of TAG and CAG 3' splice sites.Journal of human genetics · 2025Article
- Genome-Wide Identification of Alternative Splicing inMicroorganisms · 2025Article
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Regulatory activity is the default DNA state in eukaryotes.Nature structural & molecular biology · 2024Article
- Exonic splicing code and coordination of divalent metals in proteins.Nucleic acids research · 2024Article
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.RNA (New York, N.Y.) · 2024Article
- Deciphering the role of alternative splicing in neoplastic diseases for immune-oncological therapies.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA splicing is a key process in eukaryotic gene expression, in which an intron is spliced out of a pre-mRNA molecule to eventually produce a mature mRNA. Most intron-containing genes are constitutively spliced, hence efficient splicing of an intron is crucial for efficient regulation of gene expression. Here we use a large synthetic oligo library of ~20,000 variants to explore how different intronic sequence features affect splicing efficiency and mRNA expression levels in S. cerevisiae. Introns are defined by three functional sites, the 5' donor site, the branch site, and the 3' acceptor site. Using a combinatorial design of synthetic introns, we demonstrate how non-consensus splice site sequences in each of these sites affect splicing efficiency. We then show that S. cerevisiae splicing machinery tends to select alternative 3' splice sites downstream of the original site, and we suggest that this tendency created a selective pressure, leading to the avoidance of cryptic splice site motifs near introns' 3' ends. We further use natural intronic sequences from other yeast species, whose splicing machineries have diverged to various extents, to show how intron architectures in the various species have been adapted to the organism's splicing machinery. We suggest that the observed tendency for cryptic splicing is a result of a loss of a specific splicing factor, U2AF1. Lastly, we show that synthetic sequences containing two introns give rise to alternative RNA isoforms in S. cerevisiae, demonstrating that merely a synthetic fusion of two introns might be suffice to facilitate alternative splicing in yeast. Our study reveals novel mechanisms by which introns are shaped in evolution to allow cells to regulate their transcriptome. In addition, it provides a valuable resource to study the regulation of constitutive and alternative splicing in a model organism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.