ArticleNature communications2024
Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Review
- Cotranslational membrane protein biogenesis by an EMC-bound translocon.Nature structural & molecular biology · 2026Article
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- An upstream open reading frame represses translation of the neuronal potassium channel KCNQ2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Micropeptides encoded by lncRNAs associated with cancer progression reveal novel immunogenic epitopes.Bioinformatics (Oxford, England) · 2026Article
- Ribo-ITP enables identification of translons from limited input samples.Nature communications · 2026Article
- STREMI: a dual-function upstream ORF-encoded regulator of mitochondrial cristae architecture.EMBO reports · 2026Article
- A Proteogenomic Approach to Discover Novel lncRNA-Derived Microproteins and Their Potential Clinical Utility in Hepatocellular Carcinoma.Molecular & cellular proteomics : MCP · 2026Article
- An expanded reference catalog of translated open reading frames for biomedical research.Nucleic acids research · 2026Article
- Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development.Experimental & molecular medicine · 2026Review
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 2026Article
- Review
- Placenta-Driven Evolution: Viral Gene Acquisition andBiomolecules · 2026Review
- RNA G-quadruplexes promote codon repeat-associated ribosomal frameshifting in human genes.Nucleic acids research · 2026Article
- riboCIRC v2.0: an expanded resource for translatable CircRNAs.Nucleic acids research · 2026Article
- Computational Discovery of Angiotensin-(1-7)-like Peptides Targeting the MAS Receptor from the Genomic Dark Matter ofInternational journal of medical sciences · 2026Article
- Article
- Microproteins: Uncovering Hidden Layers of the Proteome.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Approaches for identification of 5' UTR mutations impacting translation and protein production from neurodevelopmental disorder genes.Cell reports methods · 2025Article
- The 'non-conventional' peptidome: A new layer in plant regulatory mechanisms.Plant communications · 2025Review
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5 authors.
Funding
Abstract
Studies have revealed dozens of functional peptides in putative 'noncoding' regions and raised the question of how many proteins are encoded by noncanonical open reading frames (ORFs). Here, we comprehensively annotate genome-wide translated ORFs across five eukaryotes (human, mouse, zebrafish, worm, and yeast) by analyzing ribosome profiling data. We develop a logistic regression model named PepScore based on ORF features (expected length, encoded domain, and conservation) to calculate the probability that the encoded peptide is stable in humans. Systematic ectopic expression validates PepScore and shows that stable complex-associating microproteins can be encoded in 5'/3' untranslated regions and overlapping coding regions of mRNAs besides annotated noncoding RNAs. Stable noncanonical proteins follow conventional rules and localize to different subcellular compartments. Inhibition of proteasomal/lysosomal degradation pathways can stabilize some peptides especially those with moderate PepScores, but cannot rescue the expression of short ones with low PepScores suggesting they are directly degraded by cellular proteases. The majority of human noncanonical peptides with high PepScores show longer lengths but low conservation across species/mammals, and hundreds contain trait-associated genetic variants. Our study presents a statistical framework to identify stable noncanonical peptides in the genome and provides a valuable resource for functional characterization of noncanonical translation during development and disease.
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