ArticleNature genetics2024
Global impact of unproductive splicing on human gene expression.
Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Familial acromegaly with a novelJCEM case reports · 2026Article
- Pervasive noise in human pre-mRNA splice site selection.Molecular cell · 2026Article
- Genome-Wide Analysis of Alternative Splicing Identifies a Prognostic Signature in ER-Positive Breast Cancer.Genes · 2026Article
- The U1 snRNP protein U1C and Helix H of U1 snRNA are critical for small molecule splicing modulator function.Nature communications · 2026Article
- The splice of life: an isoform-centric view of disease, technology, and therapeutics.The Journal of clinical investigation · 2026Review
- Data-driven RNA phenotyping captures genetically regulated dimensions of the transcriptome.American journal of human genetics · 2026Article
- Neuron type-specific translatomes in dorsal hippocampus during early memory consolidation.Nature communications · 2026Article
- Intron location and sequence modulate gene expression in Yarrowia lipolytica.Nucleic acids research · 2026Article
- Alternative Splicing of SCL30a Generates Distinct Isoforms to Modulate ABA Signaling in Arabidopsis.Plants (Basel, Switzerland) · 2026Article
- Novel examples of NMD escape through alternative intronic polyadenylation.NAR genomics and bioinformatics · 2026Article
- Shared splicing dysregulation in heart failure associated with dilated and ischaemic cardiomyopathy and spatial specificity across cardiac regions.Cardiovascular research · 2026Article
- Orthrus: toward evolutionary and functional RNA foundation models.Nature methods · 2026Article
- Alternative splicing-triggered mRNA decay informs splice-switching targets for neurodevelopmental disorders.The Journal of clinical investigation · 2026Article
- Pervasive non-triplet alternative splicing drives functional isoform diversity.Nature communications · 2026Article
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- A homozygous synonymous variant in SMG5, encoding a nonsense-mediated mRNA decay factor, causes developmental delay with growth retardation and relative macrocephaly.Human genetics · 2026Article
- Data-driven RNA phenotyping captures genetically regulated dimensions of the transcriptome.bioRxiv : the preprint server for biology · 2026Article
- Opportunities for RNA sequencing in physiology: from big data to understanding homeostasis and heterogeneity.Function (Oxford, England) · 2026Review
- Impact of disease-associated chromatin accessibility QTLs across immune cell types and contexts.Cell genomics · 2026Article
- Long non-coding RNAs in glioblastoma: from molecular drivers to therapeutic targets.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Alternative splicing (AS) in human genes is widely viewed as a mechanism for enhancing proteomic diversity. AS can also impact gene expression levels without increasing protein diversity by producing 'unproductive' transcripts that are targeted for rapid degradation by nonsense-mediated decay (NMD). However, the relative importance of this regulatory mechanism remains underexplored. To better understand the impact of AS-NMD relative to other regulatory mechanisms, we analyzed population-scale genomic data across eight molecular assays, covering various stages from transcription to cytoplasmic decay. We report threefold more unproductive splicing compared with prior estimates using steady-state RNA. This unproductive splicing compounds across multi-intronic genes, resulting in 15% of transcript molecules from protein-coding genes being unproductive. Leveraging genetic variation across cell lines, we find that GWAS trait-associated loci explained by AS are as often associated with NMD-induced expression level differences as with differences in protein isoform usage. Our findings suggest that much of the impact of AS is mediated by NMD-induced changes in gene expression rather than diversification of the proteome.
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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.