m6A RNA methylation facilitates pre-mRNA 3'-end formation and is essential for viability of Toxoplasma gondii.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
25
01
2021
accepted:
16
07
2021
revised:
10
08
2021
pubmed:
30
7
2021
medline:
25
2
2023
entrez:
29
7
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34324585
doi: 10.1371/journal.ppat.1009335
pii: PPATHOGENS-D-21-00196
pmc: PMC8354455
doi:
Substances chimiques
RNA, Messenger
0
Methyltransferases
EC 2.1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009335Subventions
Organisme : NIAID NIH HHS
ID : R01 AI124723
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI145239
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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