ArticleProceedings of the National Academy of Sciences of the United States of America2010
Dual coding in alternative reading frames correlates with intrinsic protein disorder.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Transcript isoform switching during embryonic and post-hatch development of broiler breast muscle.Poultry science · 2026Article
- Human SRD5A1 as a case of gene expression indel-resistance in triple-coding region.Genome biology · 2026Article
- Pervasive non-triplet alternative splicing drives functional isoform diversity.Nature communications · 2026Article
- SyMetrics: an integrated machine learning model for evaluating the pathogenicity of synonymous variants in the human genome.NAR genomics and bioinformatics · 2026Article
- Alternatively Spliced Dual-Coding Regions Contribute to the Human Gene Regulatory Program.bioRxiv : the preprint server for biology · 2026Article
- Hallmarks of cellular senescence: biology, mechanisms, regulations.Experimental & molecular medicine · 2025Review
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Design of overlapping genes using deep generative models of protein sequences.bioRxiv : the preprint server for biology · 2025Article
- Detection of mRNA Transcript Variants.Genes · 2025Review
- Translation of Overlapping Open Reading Frames Promoted by Type 2 IRESs in Avian Calicivirus Genomes.Viruses · 2024Article
- Overlaps Between CDS Regions of Protein-Coding Genes in the Human Genome: A Case Study on the NR1D1-THRA Gene Pair.Journal of molecular evolution · 2023Article
- Analysis of nested alternate open reading frames and their encoded proteins.NAR genomics and bioinformatics · 2022Article
- OpenVar: functional annotation of variants in non-canonical open reading frames.Cell & bioscience · 2022Article
- The FUS gene is dual-coding with both proteins contributing to FUS-mediated toxicity.EMBO reports · 2021Article
- Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene.Virus evolution · 2021Review
- Splicing-accessible coding 3'UTRs control protein stability and interaction networks.Genome biology · 2020Article
- Article
- Dynamic Alternative Splicing During Mouse Preimplantation Embryo Development.Frontiers in bioengineering and biotechnology · 2020Article
- A Secreted RNA Binding Protein Forms RNA-Stabilizing Granules in the Honeybee Royal Jelly.Molecular cell · 2019Article
- Robustness by intrinsically disordered C-termini and translational readthrough.Nucleic acids research · 2018Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous human genes display dual coding within alternatively spliced regions, which give rise to distinct protein products that include segments translated in more than one reading frame. To resolve the ensuing protein structural puzzle, we identified 67 human genes with alternative splice variants comprising a dual-coding region at least 75 nucleotides in length and analyzed the structural status of the protein segments they encode. The inspection of their amino acid composition and predictions by the IUPred and PONDR VSL2 algorithms suggest a high propensity for structural disorder in dual-coding regions. In the case of +1 frameshifts, the average level of disorder in the two frames is similarly high (47.2% in the ancestral frame, 58.2% in the derived frame, with the average level of disorder in human proteins being approximately 30%), whereas in the case of -1 frameshifts, there is a significant tendency to become more disordered upon shifting the frame (16.7% in the ancestral frame, 56.3% in the derived frame). The regions encoded by the derived frame are mostly disordered (disorder percentage > 50%) in 39 out of 62 cases, which strongly suggests that structural disorder enables these protein products to exist and function without the need of a highly evolved 3D fold. The potential advantages are also demonstrated by the appearance of novel functions and the high incidence of transcripts escaping nonsense-mediated decay. By discussing several examples, we demonstrate that dual coding may be an effective mechanism for the evolutionary appearance of novel intrinsically disordered regions with new functions.
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