ArticleNature communications2021
Disrupting upstream translation in mRNAs is associated with human disease.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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.
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Who cites it
48 citing papers in PubMed, 68 citations in OpenAlex.
- Global translational reprogramming inVirulence · 2026Article
- Site-specific inhibition of translation initiation via 2'-O-methylation.Nucleic acids research · 2026Article
- The long non-coding RNA-encoded microprotein MKKS3 drives colorectal cancer chemoresistance.Experimental & molecular medicine · 2026Article
- Ribo-ITP enables identification of translons from limited input samples.Nature communications · 2026Article
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- The birth, death, and evolutionary compensation of uORFs in Drosophila.Nucleic acids research · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.RNA biology · 2025Review
- A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure.Genome medicine · 2025Article
- Loss of non-canonical translation initiation factors impairs perinatal cardiac function in mice.Experimental animals · 2025Article
- Alternative splicing generates HER2 isoform diversity underlying antibody-drug conjugate resistance in breast cancer.Genome research · 2025Article
- Article
- RIBOSS detects novel translational events by combining long- and short-read transcriptome and translatome profiling.Briefings in bioinformatics · 2025Article
- Enhancing the annotation of small ORF-altering variants using MORFEE: introducing MORFEEdb, a comprehensive catalog of SNVs affecting upstream ORFs in human 5'UTRs.NAR genomics and bioinformatics · 2025Article
- The cryptic lncRNA-encoded microprotein TPM3P9 drives oncogenic RNA splicing and tumorigenesis.Signal transduction and targeted therapy · 2025Article
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- Tiny but mighty: Diverse functions of uORFs that regulate gene expression.Computational and structural biotechnology journal · 2024Review
- Non-canonical translation in cancer: significance and therapeutic potential of non-canonical ORFs, mCell death discovery · 2024Review
- Coding, or non-coding, that is the question.Cell research · 2024Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Ribosome-profiling has uncovered pervasive translation in non-canonical open reading frames, however the biological significance of this phenomenon remains unclear. Using genetic variation from 71,702 human genomes, we assess patterns of selection in translated upstream open reading frames (uORFs) in 5'UTRs. We show that uORF variants introducing new stop codons, or strengthening existing stop codons, are under strong negative selection comparable to protein-coding missense variants. Using these variants, we map and validate gene-disease associations in two independent biobanks containing exome sequencing from 10,900 and 32,268 individuals, respectively, and elucidate their impact on protein expression in human cells. Our results suggest translation disrupting mechanisms relating uORF variation to reduced protein expression, and demonstrate that translation at uORFs is genetically constrained in 50% of human genes.
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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.