ArticleNature communications2024
Quantifying negative selection in human 3' UTRs uncovers constrained targets of RNA-binding proteins.
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 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- RNA-Binding Proteins Regulate Cardiovascular Disease Progression Through Alternative Splicing and Alternative Polyadenylation.Journal of cardiovascular translational research · 2026Review
- The quantitative impact of 3'UTRs on gene expression.Nucleic acids research · 2025Article
- Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease.Genome medicine · 2025Article
- Article
- Context-adjusted proportion of singletons (CAPS): a novel metric for assessing negative selection in the human genome.NAR genomics and bioinformatics · 2024Article
- Regulatory features aid interpretation of 3'UTR variants.American journal of human genetics · 2024Article
- Improved modeling of RNA-binding protein motifs in an interpretable neural model of RNA splicing.Genome biology · 2024Article
- Genome-wide identification of dominant polyadenylation hexamers for use in variant classification.Human molecular genetics · 2023Article
- Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning.Genome biology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Many non-coding variants associated with phenotypes occur in 3' untranslated regions (3' UTRs), and may affect interactions with RNA-binding proteins (RBPs) to regulate gene expression post-transcriptionally. However, identifying functional 3' UTR variants has proven difficult. We use allele frequencies from the Genome Aggregation Database (gnomAD) to identify classes of 3' UTR variants under strong negative selection in humans. We develop intergenic mutability-adjusted proportion singleton (iMAPS), a generalized measure related to MAPS, to quantify negative selection in non-coding regions. This approach, in conjunction with in vitro and in vivo binding data, identifies precise RBP binding sites, miRNA target sites, and polyadenylation signals (PASs) under strong selection. For each class of sites, we identify thousands of gnomAD variants under selection comparable to missense coding variants, and find that sites in core 3' UTR regions upstream of the most-used PAS are under strongest selection. Together, this work improves our understanding of selection on human genes and validates approaches for interpreting genetic variants in human 3' UTRs.
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Registered trials
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