Evidence map›Paper›PMID 29099293›Full record

ArticleRNA biology2018

Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme.

Isabel C Vallecillo-Viejo, Noa Liscovitch-Brauer, Maria Fernanda Montiel-Gonzalez, Eli Eisenberg, Joshua J C Rosenthal

Open access · bronzeAbstract read
In one paragraph

Article in RNA biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
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

59 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
  2. A Translational Roadmap for Neurological Nonsense Mutation Disorders.International journal of molecular sciences · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. An ADAR2-mimic base editor for efficient C-to-U RNA editing in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Emerging clinical applications of ADAR based RNA editing.Stem cells translational medicine · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Programmable RNA writing with trans-splicing.bioRxiv : the preprint server for biology · 2024
    Article
  19. Review
  20. 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 at 2 institutions in 3 countries.

Isabel C Vallecillo-Viejoa Eugene Bell Center for Regenerative Biology and Tissue Engineering , The Marine Biological Laboratory , Woods Hole , MA , USA.
Noa Liscovitch-Brauerc Raymond and Beverly Sackler School of Physics and Astronomy , Tel Aviv University , Tel Aviv , Israel.
Maria Fernanda Montiel-Gonzaleza Eugene Bell Center for Regenerative Biology and Tissue Engineering , The Marine Biological Laboratory , Woods Hole , MA , USA.ORCID 0000-0002-3745-2719
Eli Eisenbergc Raymond and Beverly Sackler School of Physics and Astronomy , Tel Aviv University , Tel Aviv , Israel.
Joshua J C Rosenthala Eugene Bell Center for Regenerative Biology and Tissue Engineering , The Marine Biological Laboratory , Woods Hole , MA , USA.ORCID 0000-0001-8139-9364
Marine Biological Laboratory · USTel Aviv University · IL

Funding

Site-directed RNA editing: a new method to correct disease causing mutationsR01NS087726 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ADELMAN, JOHN P, BREHM, PAUL · 2013 to 2017
$3.4M
NINDS NIH HHS R01 NS087726
6 · The paper itself

Abstract

Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.

Indexed as

Mutagenesis, Site-DirectedAdenosineCodon, NonsenseCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHumansInosineMutationRNA EditingRNA, Guide, CRISPR-Cas SystemsTranscriptomeTransfectionAdenosineCFTR protein, humanCodon, NonsenseCystic Fibrosis Transmembrane Conductance RegulatorInosineRNA, Guide, CRISPR-Cas SystemsADARoff-target RNA editingRNA editingsite-directed RNA editing

Identifiers

PMID29099293
PMCPMC5786015
OpenAlexW2765186092

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.