Evidence map›Paper›PMID 35190939›Full record

ArticleVirus genes2022

Overexpression of m6A-factors METTL3, ALKBH5, and YTHDC1 alters HPV16 mRNA splicing.

Xiaoxu Cui, Kersti Nilsson, Naoko Kajitani, Stefan Schwartz

Abstract read
In one paragraph

Article in Virus genes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Ghost authors revealed: The structure and function of human NWiley interdisciplinary reviews. RNA · 2023
    Review
  6. Review
  7. Splice site mPeerJ · 2023
    Article
  8. Article
  9. NFrontiers in immunology · 2022
    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.

Xiaoxu CuiDepartment of Laboratory Medicine, Lund University, BMC-B13, 221 84, Lund, Sweden.
Kersti NilssonDepartment of Laboratory Medicine, Lund University, BMC-B13, 221 84, Lund, Sweden.
Naoko KajitaniDepartment of Medical Biochemistry and Microbiology, Uppsala University, BMC-B9, 751 23, Uppsala, Sweden.
Stefan SchwartzDepartment of Medical Biochemistry and Microbiology, Uppsala University, BMC-B9, 751 23, Uppsala, Sweden. stefan.schwartz@imbim.uu.se.ORCID http://orcid.org/0000-0002-1249-0575

Funding

Cancerfonden CAN2018/702China Scholarship Council 201809120016Vetenskapsrådet VR2019-01210
6 · The paper itself

Abstract

We report that overexpression of the m6A-demethylase alkB homolog 5 RNA demethylase (ALKBH5) promoted production of intron retention on the human papillomavirus type 16 (HPV16) E6 mRNAs thereby promoting E6 mRNA production. ALKBH5 also altered alternative splicing of the late L1 mRNA by an exon skipping mechanism. Knock-down of ALKBH5 had the opposite effect on splicing of these HPV16 mRNAs. Overexpression of the m6A-methylase methyltransferase-like protein 3 (METLL3) induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of the nuclear m6A-"reader" YTH domain-containing protein 1 (YTHDC1), enhanced retention of the E6-encoding intron and promoted E6 mRNA production. We also show that HPV16 mRNAs are bound to YTHDC1 in human cells and that YTHDC1 affected splicing of HPV16 E6/E7 mRNAs produced from the episomal form of the HPV16 genome. Finally, we show that HPV16 mRNAs are m6A-methylated in tonsillar cancer cells. In summary, HPV16 mRNAs are methylated in HPV16-infected tonsillar cancer cells and overexpression of m6A-"writer" METTL3, m6A-"eraser" ALKBH5 and the m6A-"reader" YTHDC1 affected HPV16 mRNA splicing, suggesting that m6A plays an important role in the HPV16 gene expression program, at least in cancer cells.

Indexed as

Papillomavirus InfectionsRNA SplicingAlkB Homolog 5, RNA DemethylaseHumansIntronsMethyltransferasesNerve Tissue ProteinsRNARNA, MessengerRNA Splicing FactorsALKBH5 protein, humanAlkB Homolog 5, RNA DemethylaseMethyltransferasesMETTL3 protein, humanNerve Tissue ProteinsRNARNA, MessengerRNA Splicing FactorsYTHDC1 protein, humanALKBH5Human papillomavirusm6AMETTL3SplicingYTHDC1

Identifiers

PMID35190939
PMCPMC8948141

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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.