ArticleProceedings of the National Academy of Sciences of the United States of America2006
Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
232 citing papers in PubMed.
- Article
- Alternative splicing fine-tunes modular protein interfaces to control protein localization.Nature structural & molecular biology · 2026Article
- MYB Factors: Hubs of Plant Stress and Hormone Crosstalk.Plant biotechnology journal · 2026Review
- The allostery principle supports the symbolic character of signaling circuits: gene regulation provides a form of intelligence to living systems.Theory in biosciences = Theorie in den Biowissenschaften · 2026Article
- MASQ: A multiplex qPCR platform for quantitative alternative splicing analysis in clinical specimens.Molecular therapy. Nucleic acids · 2026Article
- Prevalence and Functional Roles of Intrinsic Disorder in the [F-actin]-monooxygenase MICAL Family Members and their Interactors.Cell biochemistry and biophysics · 2026Article
- Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All.International journal of molecular sciences · 2026Review
- Pervasive non-triplet alternative splicing drives functional isoform diversity.Nature communications · 2026Article
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Alternatively Spliced Dual-Coding Regions Contribute to the Human Gene Regulatory Program.bioRxiv : the preprint server for biology · 2026Article
- Global Analysis of mRNA Alternative Splicing in the Trigeminal Ganglion at Different Stages of Trigeminal Neuropathic Pain in Mice.Journal of pain research · 2026Article
- Isoforms in action: The impact of transcript diversity in phenotype.Genetics and molecular biology · 2026Article
- Integrative Multi-Omics Characterization and Structural Insights into the Poorly Annotated IntegrinGenes · 2025Article
- Predicting the structural impact of human alternative splicing.Genome biology · 2025Article
- Hallmarks of cellular senescence: biology, mechanisms, regulations.Experimental & molecular medicine · 2025Review
- Flexible iron: disorder in the ironome brings order to protein structure and function.Frontiers in molecular biosciences · 2025Article
- RNA splicing in bone diseases: mechanisms, pathogenesis and therapeutics.Acta biochimica Polonica · 2025Review
- On the Roles of Protein Intrinsic Disorder in the Origin of Life and Evolution.Life (Basel, Switzerland) · 2024Review
- VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation.Orphanet journal of rare diseases · 2024Review
- Splicing regulation through biomolecular condensates and membraneless organelles.Nature reviews. Molecular cell biology · 2024Review
172 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Alternative splicing of pre-mRNA generates two or more protein isoforms from a single gene, thereby contributing to protein diversity. Despite intensive efforts, an understanding of the protein structure-function implications of alternative splicing is still lacking. Intrinsic disorder, which is a lack of equilibrium 3D structure under physiological conditions, may provide this understanding. Intrinsic disorder is a common phenomenon, particularly in multicellular eukaryotes, and is responsible for important protein functions including regulation and signaling. We hypothesize that polypeptide segments affected by alternative splicing are most often intrinsically disordered such that alternative splicing enables functional and regulatory diversity while avoiding structural complications. We analyzed a set of 46 differentially spliced genes encoding experimentally characterized human proteins containing both structured and intrinsically disordered amino acid segments. We show that 81% of 75 alternatively spliced fragments in these proteins were associated with fully (57%) or partially (24%) disordered protein regions. Regions affected by alternative splicing were significantly biased toward encoding disordered residues, with a vanishingly small P value. A larger data set composed of 558 SwissProt proteins with known isoforms produced by 1,266 alternatively spliced fragments was characterized by applying the pondr vsl1 disorder predictor. Results from prediction data are consistent with those obtained from experimental data, further supporting the proposed hypothesis. Associating alternative splicing with protein disorder enables the time- and tissue-specific modulation of protein function needed for cell differentiation and the evolution of multicellular organisms.
Indexed as
Identifiers
What OpenQuestion holds
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.