Evidence map›Paper›PMID 35353638›Full record

ArticleThe CRISPR journal2022

Combined Theoretical, Bioinformatic, and Biochemical Analyses of RNA Editing by Adenine Base Editors.

Kartik L Rallapalli, Brodie L Ranzau, Kaushik R Ganapathy, Francesco Paesani, Alexis C Komor

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The CRISPR journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Kartik L RallapalliDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA; University of California San Diego, La Jolla, California, USA.
Brodie L RanzauDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA; University of California San Diego, La Jolla, California, USA.
Kaushik R GanapathyHalıcıoğlu Data Science Institute, University of California San Diego, La Jolla, California, USA; University of California San Diego, La Jolla, California, USA.
Francesco PaesaniDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA; University of California San Diego, La Jolla, California, USA.
Alexis C KomorDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA; University of California San Diego, La Jolla, California, USA.

Funding

Supplement to R35 "Development and Application of New Genome Editing Tools for the Functional Investigation of Genetic Variants of Uncertain Significance"R35GM138317 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alexis C. Komor · 2020 to 2026
$2.8M
Chemistry-Biology Interfaces at UCSDT32GM146648 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael D. Burkart, Alexis C. Komor · 2022 to 2026
$876k
Chemical Biology Interfaces at UC San DiegoT32GM112584 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BURKART, MICHAEL D. · 2015 to 2019
$729k
Development of New Genome Editing Agents Using RNA Modifying EnzymesR21GM135736 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMOR, ALEXIS C. · 2019 to 2019
$205k
NIGMS NIH HHS R21 GM135736NIGMS NIH HHS R35 GM138317NIGMS NIH HHS T32 GM112584NIGMS NIH HHS T32 GM146648
6 · The paper itself

Abstract

Adenine base editors (ABEs) have been subjected to multiple rounds of mutagenesis with the goal of optimizing their function as efficient and precise genome editing agents. Despite an ever-expanding data set of ABE mutants and their corresponding DNA or RNA-editing activity, the molecular mechanisms defining these changes remain to be elucidated. In this study, we provide a systematic interpretation of the nature of these mutations using an entropy-based classification model that relies on evolutionary data from extant protein sequences. Using this model in conjunction with experimental analyses, we identify two previously reported mutations that form an epistatic pair in the RNA-editing functional landscape of ABEs. Molecular dynamics simulations reveal the atomistic details of how these two mutations affect substrate-binding and catalytic activity, via both individual and cooperative effects, hence providing insights into the mechanisms through which these two mutations are epistatically coupled.

Indexed as

Gene EditingRNA EditingAdenineComputational BiologyCRISPR-Cas SystemsRNAAdenineRNA

Identifiers

PMID35353638
PMCPMC9347300

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.