Evidence map›Paper›PMID 29659627›Full record

ArticlePLoS pathogens2018

N6-methyladenosine modification and the YTHDF2 reader protein play cell type specific roles in lytic viral gene expression during Kaposi's sarcoma-associated herpesvirus infection.

Charles R Hesser, John Karijolich, Dan Dominissini, Chuan He, Britt A Glaunsinger

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 1 pooled it
9.4field-weighted citation impact, top 1% 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

137 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.

  1. Pooled it
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  13. The role of NJournal of virology · 2025
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  19. Epitranscriptomic mScience advances · 2024
    Article
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77 more citing papers are in PubMed but not listed here.

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 4 institutions in 2 countries.

Charles R HesserDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States of America.ORCID 0000-0002-6690-3283
John KarijolichDepartment of Plant & Microbial Biology, University of California Berkeley, Berkeley, CA, United States of America.ORCID 0000-0002-7925-1122
Dan DominissiniDepartment of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, United States of America.
Chuan HeDepartment of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, United States of America.
Britt A GlaunsingerDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States of America.ORCID 0000-0003-0479-9377
Howard Hughes Medical Institute · USTel Aviv University · ILUniversity of California, Berkeley · USVanderbilt University Medical Center · US

Funding

Regulation of Gammaherpesviral Late Gene ExpressionR01AI122528 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI Britt A Glaunsinger · 2016 to 2026
$4.2M
Base-resolution sequencing of m6A in RNAR01HG008688 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2015 to 2017
$1.3M
NHGRI NIH HHS R01 HG008688NIAID NIH HHS R01 AI122528NIH HHS HG008688
6 · The paper itself

Abstract

Methylation at the N6 position of adenosine (m6A) is a highly prevalent and reversible modification within eukaryotic mRNAs that has been linked to many stages of RNA processing and fate. Recent studies suggest that m6A deposition and proteins involved in the m6A pathway play a diverse set of roles in either restricting or modulating the lifecycles of select viruses. Here, we report that m6A levels are significantly increased in cells infected with the oncogenic human DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV). Transcriptome-wide m6A-sequencing of the KSHV-positive renal carcinoma cell line iSLK.219 during lytic reactivation revealed the presence of m6A across multiple kinetic classes of viral transcripts, and a concomitant decrease in m6A levels across much of the host transcriptome. However, we found that depletion of the m6A machinery had differential pro- and anti-viral impacts on viral gene expression depending on the cell-type analyzed. In iSLK.219 and iSLK.BAC16 cells the pathway functioned in a pro-viral manner, as depletion of the m6A writer METTL3 and the reader YTHDF2 significantly impaired virion production. In iSLK.219 cells the defect was linked to their roles in the post-transcriptional accumulation of the major viral lytic transactivator ORF50, which is m6A modified. In contrast, although the ORF50 mRNA was also m6A modified in KSHV infected B cells, ORF50 protein expression was instead increased upon depletion of METTL3, or, to a lesser extent, YTHDF2. These results highlight that the m6A pathway is centrally involved in regulating KSHV gene expression, and underscore how the outcome of this dynamically regulated modification can vary significantly between cell types.

Indexed as

RNA Processing, Post-TranscriptionalAdenosineB-LymphocytesCarcinoma, Renal CellCells, CulturedHEK293 CellsHerpesvirus 8, HumanHumansKidney NeoplasmsMethyltransferasesRNA-Binding ProteinsSarcoma, KaposiVirus LatencyVirus ReplicationAdenosineMethyltransferasesMETTL3 protein, humanN-methyladenosineRNA-Binding ProteinsYTHDF2 protein, human

Identifiers

PMID29659627
PMCPMC5919695
OpenAlexW2953224225

What OpenQuestion holds

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LicenceCC BY
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.