ArticleNature genetics2020
RNA isoform screens uncover the essentiality and tumor-suppressor activity of ultraconserved poison exons.
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed.
- An antisense antidote to oncogenic poison exons.Genes & development · 2026Article
- Tools and tactics for studying alternative splicing.Nature reviews. Genetics · 2026Review
- Uncovering the isoform-resolution kinetic landscape of nonsense-mediated mRNA decay with EZbakR.Genome biology · 2026Article
- Splicing of ultraconserved poison exons controls mitotic fidelity and stem cell viability.bioRxiv : the preprint server for biology · 2026Article
- Pervasive non-triplet alternative splicing drives functional isoform diversity.Nature communications · 2026Article
- Splice isoform-perturbation coupled to single cell transcriptome profiling reveals functions of microexons in neurogenesis and autism-linked pathways.Nature communications · 2026Article
- RNA-coupled CRISPR screens reveal ZNF207 as a regulator of LMNA aberrant splicing in progeria.Molecular cell · 2026Article
- Nonsense-mediated mRNA decay and associated splicing patterns in neurodevelopmental disorders.Frontiers in molecular biosciences · 2026Review
- Ultra-Conserved Poison Exons Enable Rapid and Safe Splicing Factor Gene Expression Switches: A Hypothesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Direct and indirect effects of spliceosome disruption compromise gene regulation by nonsense-mediated mRNA decay.RNA biology · 2025Article
- A portable poison exon for small-molecule control of mammalian gene expression.Nature methods · 2025Article
- Roles of No-Go RNA decay in the control of plant viruses and transposable elements.BMC plant biology · 2025Review
- Cas13d-mediated isoform-specific RNA knockdown with a unified computational and experimental toolbox.Nature communications · 2025Article
- Review
- Antisense oligonucleotide-mediated TRA2β poison exon inclusion induces the expression of a lncRNA with anti-tumor effects.Nature communications · 2025Article
- CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells.Scientific reports · 2025Article
- Article
- Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024Review
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Alternative Splicing: A Potential Therapeutic Target in Hematological Malignancies.Hematology reports · 2024Review
13 more citing papers are in PubMed but not listed here.
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13 authors.
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Abstract
While RNA-seq has enabled comprehensive quantification of alternative splicing, no correspondingly high-throughput assay exists for functionally interrogating individual isoforms. We describe pgFARM (paired guide RNAs for alternative exon removal), a CRISPR-Cas9-based method to manipulate isoforms independent of gene inactivation. This approach enabled rapid suppression of exon recognition in polyclonal settings to identify functional roles for individual exons, such as an SMNDC1 cassette exon that regulates pan-cancer intron retention. We generalized this method to a pooled screen to measure the functional relevance of 'poison' cassette exons, which disrupt their host genes' reading frames yet are frequently ultraconserved. Many poison exons were essential for the growth of both cultured cells and lung adenocarcinoma xenografts, while a subset had clinically relevant tumor-suppressor activity. The essentiality and cancer relevance of poison exons are likely to contribute to their unusually high conservation and contrast with the dispensability of other ultraconserved elements for viability.
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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.