Evidence map›Paper›PMID 34324585›Full record

ArticlePLoS pathogens2021

m6A RNA methylation facilitates pre-mRNA 3'-end formation and is essential for viability of Toxoplasma gondii.

Michael J Holmes, Leah R Padgett, Matheus S Bastos, William J Sullivan

Abstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
  2. Review
  3. NResearch (Washington, D.C.) · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. NAT10-mediated mRNAScience advances · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Pseudouridine andRSC chemical biology · 2024
    Review
  12. Ghost authors revealed: The structure and function of human NWiley interdisciplinary reviews. RNA · 2023
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Epitranscriptome profiling of spleen mRNA mFrontiers in immunology · 2022
    Article
  18. 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

4 authors.

Michael J HolmesDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.ORCID 0000-0002-4562-287X
Leah R PadgettDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Matheus S BastosDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.ORCID 0000-0002-1834-6005
William J SullivanDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.ORCID 0000-0003-1823-8642

Funding

Translational control during stage conversion of Toxoplasma, an opportunistic infection of HIV/AIDSR01AI124723 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI SULLIVAN, WILLIAM J, WEK, RONALD C · 2016 to 2020
$2.0M
Epitranscriptomics in the AIDS-opportunistic pathogen Toxoplasma gondiiR21AI145239 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI SULLIVAN, WILLIAM J · 2019 to 2020
$426k
NIAID NIH HHS R01 AI124723NIAID NIH HHS R21 AI145239
6 · The paper itself

Abstract

Toxoplasma gondii is an obligate intracellular parasite that can cause serious opportunistic disease in the immunocompromised or through congenital infection. To progress through its life cycle, Toxoplasma relies on multiple layers of gene regulation that includes an array of transcription and epigenetic factors. Over the last decade, the modification of mRNA has emerged as another important layer of gene regulation called epitranscriptomics. Here, we report that epitranscriptomics machinery exists in Toxoplasma, namely the methylation of adenosines (m6A) in mRNA transcripts. We identified novel components of the m6A methyltransferase complex and determined the distribution of m6A marks within the parasite transcriptome. m6A mapping revealed the modification to be preferentially located near the 3'-boundary of mRNAs. Knockdown of the m6A writer components METTL3 and WTAP resulted in diminished m6A marks and a complete arrest of parasite replication. Furthermore, we examined the two proteins in Toxoplasma that possess YTH domains, which bind m6A marks, and showed them to be integral members of the cleavage and polyadenylation machinery that catalyzes the 3'-end processing of pre-mRNAs. Loss of METTL3, WTAP, or YTH1 led to a defect in transcript 3'-end formation. Together, these findings establish that the m6A epitranscriptome is essential for parasite viability by contributing to the processing of mRNA 3'-ends.

Indexed as

Cells, CulturedCell SurvivalEpigenesis, GeneticHumansMethylationMethyltransferasesRNA 3' End ProcessingRNA, MessengerToxoplasmaMethyltransferasesRNA, Messenger

Identifiers

PMID34324585
PMCPMC8354455

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Registered trials

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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.