ArticleMolecular biology and evolution2018
Human C-to-U Coding RNA Editing Is Largely Nonadaptive.
Article in Molecular biology and evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Evaluating the adaptive hypothesis of A-to-I RNA editing in filamentous ascomycete fungi.Molecular biology and evolution · 2026Article
- Deciphering APOBEC1 in Avians: unravelling loss events and functional insights.Immunogenetics · 2026Article
- Functionality versus Adaptation: Insights from Transcriptional Adaptation.Journal of molecular evolution · 2026Review
- Article
- Two codes of RNA editing by deamination in human diseases.Experimental & molecular medicine · 2026Review
- Different mRNAs encoding identical proteins: how and why?Journal of applied genetics · 2026Article
- Can transcriptome size and off-target effects explain the contrasting evolution of mitochondrial vs nuclear RNA editing?Journal of evolutionary biology · 2025Article
- The implications of alternative splicing regulation for maximum lifespan.Nature communications · 2025Article
- The Implications of Alternative Splicing Regulation for Maximum Lifespan.bioRxiv : the preprint server for biology · 2025Article
- BIRC3 RNA Editing Modulates Lipopolysaccharide-Induced Liver Inflammation: Potential Implications for Animal Health.International journal of molecular sciences · 2025Article
- Research progress on N6-methyladenosine RNA modification in osteosarcoma: functions, mechanisms, and potential clinical applications.Medical oncology (Northwood, London, England) · 2025Review
- Most m5C Modifications in Mammalian mRNAs are Nonadaptive.Molecular biology and evolution · 2025Article
- WTAP-Mediated N6-Methyladenosine Modification Promotes Gastric Cancer Progression by Regulating MAP2K6 Expression.Journal of Cancer · 2025Article
- Article
- Genetic and selective constraints on the optimization of gene product diversity.bioRxiv : the preprint server for biology · 2024Article
- GTDrift: a resource for exploring the interplay between genetic drift, genomic and transcriptomic characteristics in eukaryotes.NAR genomics and bioinformatics · 2024Article
- Article
- Regulatory effect of N6-methyladenosine on tumor angiogenesis.Frontiers in immunology · 2024Review
- Role of N6-methyladenosine methylation in glioma: recent insights and future directions.Cellular & molecular biology letters · 2023Review
- Identification and Interpretation of A-to-I RNA Editing Events in Insect Transcriptomes.International journal of molecular sciences · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
2 authors.
Funding
Abstract
C-to-U RNA editing enzymatically converts the base C to U in RNA molecules and could lead to nonsynonymous changes when occurring in coding regions. Hundreds to thousands of coding sites were recently found to be C-to-U edited or editable in humans, but the biological significance of this phenomenon is elusive. Here, we test the prevailing hypothesis that nonsynonymous editing is beneficial because it provides a means for tissue- or time-specific regulation of protein function that may be hard to accomplish by mutations due to pleiotropy. The adaptive hypothesis predicts that the fraction of sites edited and the median proportion of RNA molecules edited (i.e., editing level) are both higher for nonsynonymous than synonymous editing. However, our empirical observations are opposite to these predictions. Furthermore, the frequency of nonsynonymous editing, relative to that of synonymous editing, declines as genes become functionally more important or evolutionarily more constrained, and the nonsynonymous editing level at a site is negatively correlated with the evolutionary conservation of the site. Together, these findings refute the adaptive hypothesis; they instead indicate that the reported C-to-U coding RNA editing is mostly slightly deleterious or neutral, probably resulting from off-target activities of editing enzymes. Along with similar conclusions on the more prevalent A-to-I editing and m6A modification of coding RNAs, our study suggests that, at least in humans, most events of each type of posttranscriptional coding RNA modification likely manifest cellular errors rather than adaptations, demanding a paradigm shift in the research of posttranscriptional modification.
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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.