Evidence map›Paper›PMID 36696440›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

The fidelity of transcription in human cells.

Claire Chung, Bert M Verheijen, Xinmin Zhang, Biao Huang, Aeowynn Coakley, Eric McGann, Emily Wade, Olivia Dinep-Schneider, Jessica LaGosh, Maria-Eleni Anagnostou and 11 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Collective RNAP Dynamics Link Transcriptional Strength to Fidelity.The journal of physical chemistry letters · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Kinetic mechanisms for the sequence dependence of transcriptional errors.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
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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

21 authors at 5 institutions in 1 country.

Claire ChungUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Bert M VerheijenUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Xinmin ZhangBioinforX, Madison, WI 53719.ORCID 0000-0001-5584-2107
Biao HuangKeck School of Medicine of University of Southern California, Department of Stem Cell Biology and Regenerative Medicine, Los Angeles, CA 90033.
Aeowynn CoakleyUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Eric McGannUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Emily WadeMississippi State University, Department of Biological Sciences, Mississippi State, MS 39762.
Olivia Dinep-SchneiderMississippi State University, Department of Biological Sciences, Mississippi State, MS 39762.
Jessica LaGoshUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Maria-Eleni AnagnostouUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Stephen SimpsonUniversity of New Hampshire, Department of Molecular, Cellular, & Biomedical Sciences, Durham, NH 03824.
Kelly ThomasUniversity of New Hampshire, Department of Molecular, Cellular, & Biomedical Sciences, Durham, NH 03824.ORCID 0000-0002-0945-5269
Mimi ErnstNational Cancer Institute, Center for Cancer Research, Division of RNA Biology, Frederick, MD 21702-1201.
Allison RattrayNational Cancer Institute, Center for Cancer Research, Division of RNA Biology, Frederick, MD 21702-1201.
Michael LynchBiodesign Center for Mechanisms of Evolution, Arizona State University, Tempe, AZ 85287.ORCID 0000-0002-1653-0642
Mikhail KashlevNational Cancer Institute, Center for Cancer Research, Division of RNA Biology, Frederick, MD 21702-1201.ORCID 0000-0002-1260-6486
Berenice A BenayounUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
Zhongwei LiKeck School of Medicine of University of Southern California, Department of Stem Cell Biology and Regenerative Medicine, Los Angeles, CA 90033.
Jeffrey StrathernNational Cancer Institute, Center for Cancer Research, Division of RNA Biology, Frederick, MD 21702-1201.
Jean-Francois GoutMississippi State University, Department of Biological Sciences, Mississippi State, MS 39762.ORCID 0000-0002-4549-5647
Marc VermulstUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA 90089.
University of Southern California · USNational Cancer Institute · USMississippi State University · USUniversity of New Hampshire · USArizona State University · US

Funding

Mechanisms of transcription pausing and fidelity in prokaryotes and eukaryotesZIABC010795 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KASHLEV, MIKHAIL · 2009 to 2025
$18.1M
Causes and Population-genetic Consequences of Molecular VariationR35GM122566 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI Michael R LYNCH · 2017 to 2026
$7.7M
Understanding the role of transcription errors in aging and diseaseR01AG054641 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VERMULST, MARC · 2017 to 2021
$1.7M
NIA NIH HHS R01 AG054641NIGMS NIH HHS R35 GM122566
6 · The paper itself

Abstract

To determine the error rate of transcription in human cells, we analyzed the transcriptome of H1 human embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing of the transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species in human cells. Our results indicate that different RNA species display different error rates, suggesting that human cells prioritize the fidelity of some RNAs over others. Cross-referencing the errors that we detected with various genetic and epigenetic features of the human genome revealed that the in vivo error rate in human cells changes along the length of a transcript and is further modified by genetic context, repetitive elements, epigenetic markers, and the speed of transcription. Our experiments further suggest that BRCA1, a DNA repair protein implicated in breast cancer, has a previously unknown role in the suppression of transcription errors. Finally, we analyzed the distribution of transcription errors in multiple tissues of a new mouse model and found that they occur preferentially in neurons, compared to other cell types. These observations lend additional weight to the idea that transcription errors play a key role in the progression of various neurological disorders, including Alzheimer's disease.

Indexed as

RNATranscription, GeneticAnimalsHumansMiceProteinsRepetitive Sequences, Nucleic AcidTranscriptomeProteinsRNAAlzheimer's diseasehuman embryonic stem cellsmutagenesistranscriptiontranscription errors

Identifiers

PMID36696440
PMCPMC9945944
OpenAlexW4318025459

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.