ArticleGenome biology2024
Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
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- Beyond the gene: isoform diversity as a key contributor to human brain disorders.Current opinion in genetics & development · 2026Review
- Gene Expression and Alternative Splicing Throughout the Reproductive Cycle of a Viviparous Lizard Reveal Novel Genes for Pregnancy and Convergence With Squamates and Mammals.Molecular ecology · 2026Article
- Enhancement of Therapeutic mRNA Translation in Cellular Stress Conditions.International journal of molecular sciences · 2026Review
- 5' UTR length shapes alternative N-terminal protein isoforms across cancers and in rare disease.EMBO reports · 2026Article
- Regulatory impact of a 5'UTR resident single nucleotide variant on EDN1 gene expression and RNA-protein interactions.Scientific reports · 2026Article
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- 5' UTR length regulates alternative N-terminal protein isoform production in health and disease.bioRxiv : the preprint server for biology · 2026Article
- Modulating splicing in 5' untranslated regions to treat rare haploinsufficient disease.bioRxiv : the preprint server for biology · 2025Article
- A Cornelia de Lange syndrome NIPBL 5'-UTR mutation reduces cell proliferation in anBiomedical reports · 2025Article
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Decoding the interactions and functions of non-coding RNA with artificial intelligence.Nature reviews. Molecular cell biology · 2025Review
- The role of untranslated region variants in Mendelian disease: a review.European journal of human genetics : EJHG · 2025Review
- Discovery of NovelGenes · 2025Article
- Macroevolutionary divergence of gene expression driven by selection on protein abundance.Science (New York, N.Y.) · 2025Article
- Structural Features of 5' Untranslated Region in Translational Control of Eukaryotes.International journal of molecular sciences · 2025Review
- Transcriptome analysis of two isolates of the tomato pathogen Cladosporium fulvum, uncovers genome-wide patterns of alternative splicing during a host infection cycle.PLoS pathogens · 2024Article
- Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Dissecting non-B DNA structural motifs in untranslated regions of eukaryotic genomes.Genomics & informatics · 2024Article
- The Recent Research Progress of the Tumor mRNA Vaccine.Vaccines · 2024Review
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundUntranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5'UTRs, correlates with gene dosage sensitivity.
resultsWe investigate 5'UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5'UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5'UTR length and complexity. Genes that are most intolerant to LoF have longer 5'UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated.
conclusionsOur results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them.
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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.