ArticleMolecular cell2024
Genome-scale exon perturbation screens uncover exons critical for cell fitness.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- AltEx-BE: a tool for designing splice-site-targeting gRNAs for base editing-mediated exon skipping with exon-level annotations in diverse experimental animals.Experimental animals · 2026Article
- RBM39 modulates UPR signaling through alternative splicing of IRE1α/Genes & development · 2026Article
- Tools and tactics for studying alternative splicing.Nature reviews. Genetics · 2026Review
- Orthrus: toward evolutionary and functional RNA foundation models.Nature methods · 2026Article
- Intron Retention Controls Localization of lncRNAsbioRxiv : the preprint server for biology · 2026Article
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- Single-cell exon deletion profiling reveals splicing events that shape gene expression and cell state dynamics.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
- Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.Nature communications · 2025Article
- Orthrus: Towards Evolutionary and Functional RNA Foundation Models.bioRxiv : the preprint server for biology · 2025Article
- mtKO: A dedicated guide RNA library for mitochondria research.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025Review
- Discovering the hidden function in fungal genomes.Nature communications · 2024Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
CRISPR-Cas technology has transformed functional genomics, yet understanding of how individual exons differentially shape cellular phenotypes remains limited. Here, we optimized and conducted massively parallel exon deletion and splice-site mutation screens in human cell lines to identify exons that regulate cellular fitness. Fitness-promoting exons are prevalent in essential and highly expressed genes and commonly overlap with protein domains and interaction interfaces. Conversely, fitness-suppressing exons are enriched in nonessential genes, exhibiting lower inclusion levels, and overlap with intrinsically disordered regions and disease-associated mutations. In-depth mechanistic investigation of the screen-hit TAF5 alternative exon-8 revealed that its inclusion is required for assembly of the TFIID general transcription initiation complex, thereby regulating global gene expression output. Collectively, our orthogonal exon perturbation screens established a comprehensive repository of phenotypically important exons and uncovered regulatory mechanisms governing cellular fitness and gene expression.
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Registered trials
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.