ArticleNucleic acids research2021
Determinants of adenine-mutagenesis in diversity-generating retroelements.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Diversity-generating retroelements for programmable targeted hypermutagenesis.Nature biotechnology · 2026Article
- High-throughput analyses of a reconstituted diversity-generating retroelement identify intrinsic and extrinsic determinants of diversification.PLoS genetics · 2026Article
- Targeted protein evolution in the gut microbiome by diversity-generating retroelements.Science (New York, N.Y.) · 2025Article
- Incomplete lytic cycle of a widespread Bacteroides bacteriophage leads to the formation of defective viral particles.PLoS biology · 2025Article
- Article
- Targeted protein evolution in the gut microbiome by diversity-generating retroelements.bioRxiv : the preprint server for biology · 2024Article
- Diaminopurine in Nonenzymatic RNA Template Copying.Journal of the American Chemical Society · 2024Article
- Mechanisms used for cDNA synthesis and site-specific integration of RNA into DNA genomes by a reverse transcriptase-Cas1 fusion protein.Science advances · 2024Article
- Mechanisms used for cDNA synthesis and site-specific integration of RNA into DNA genomes by a reverse transcriptase-Cas1 fusion protein.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
4 authors.
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Abstract
Diversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial 'dark matter'. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypical Bordetella bacteriophage DGR through an in vitro system composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.
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