ArticleMolecular biology and evolution2017
Both Maintenance and Avoidance of RNA-Binding Protein Interactions Constrain Coding Sequence Evolution.
Article in Molecular biology and evolution, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.Nature communications · 2025Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
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- Synonymous variants that disrupt messenger RNA structure are significantly constrained in the human population.GigaScience · 2021Article
- Evidence for Strong Mutation Bias toward, and Selection against, U Content in SARS-CoV-2: Implications for Vaccine Design.Molecular biology and evolution · 2021Article
- Pervasive Selection against MicroRNA Target Sites in Human Populations.Molecular biology and evolution · 2020Article
- A Depletion of Stop Codons in lincRNA is Owing to Transfer of Selective Constraint from Coding Sequences.Molecular biology and evolution · 2020Article
- Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Interplay between coding and exonic splicing regulatory sequences.Genome research · 2019Article
- Post-transcriptional regulatory patterns revealed by protein-RNA interactions.Scientific reports · 2019Article
- Exonic splice regulation imposes strong selection at synonymous sites.Genome research · 2018Article
- Refining the Ambush Hypothesis: Evidence That GC- and AT-Rich Bacteria Employ Different Frameshift Defence Strategies.Genome biology and evolution · 2018Article
- Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts.Molecular biology and evolution · 2017Article
- Depletion of somatic mutations in splicing-associated sequences in cancer genomes.Genome biology · 2017Article
- ASXL gain-of-function truncation mutants: defective and dysregulated forms of a natural ribosomal frameshifting product?Biology direct · 2017Article
- Estimating the prevalence of functional exonic splice regulatory information.Human genetics · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
While the principal force directing coding sequence (CDS) evolution is selection on protein function, to ensure correct gene expression CDSs must also maintain interactions with RNA-binding proteins (RBPs). Understanding how our genes are shaped by these RNA-level pressures is necessary for diagnostics and for improving transgenes. However, the evolutionary impact of the need to maintain RBP interactions remains unresolved. Are coding sequences constrained by the need to specify RBP binding motifs? If so, what proportion of mutations are affected? Might sequence evolution also be constrained by the need not to specify motifs that might attract unwanted binding, for instance because it would interfere with exon definition? Here, we have scanned human CDSs for motifs that have been experimentally determined to be recognized by RBPs. We observe two sets of motifs-those that are enriched over nucleotide-controlled null and those that are depleted. Importantly, the depleted set is enriched for motifs recognized by non-CDS binding RBPs. Supporting the functional relevance of our observations, we find that motifs that are more enriched are also slower-evolving. The net effect of this selection to preserve is a reduction in the over-all rate of synonymous evolution of 2-3% in both primates and rodents. Stronger motif depletion, on the other hand, is associated with stronger selection against motif gain in evolution. The challenge faced by our CDSs is therefore not only one of attracting the right RBPs but also of avoiding the wrong ones, all while also evolving under selection pressures related to protein structure.
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