RNA triphosphatase-mediated mRNA capping is essential for maintaining transcript homeostasis and the survival of Toxoplasma gondii

Kalyani R. Aswale, Poonam Kashyap and Abhijit S. Deshmukh ()
Additional contact information
Kalyani R. Aswale: BRIC-National Institute of Animal Biotechnology
Poonam Kashyap: BRIC-National Institute of Animal Biotechnology
Abhijit S. Deshmukh: BRIC-National Institute of Animal Biotechnology

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract RNA modifications are crucial for gene expression in eukaryotes; however, the regulatory role of 5’ 7-methylguanosine (m7G) cap, the first modification of mRNA, remains unknown in the protozoan parasite Toxoplasma gondii. Here, we show that the mRNA capping machinery of Toxoplasma consists of three distinct enzymes: RNA triphosphatase, guanylyltransferase, and guanine-N7-methyltransferase, which together add m7G cap to RNA, recognized by cap-binding protein, TgeIF4E. Biochemical and genetic studies show that among three capping enzymes, RNA triphosphatase (TgCet) is unique and a member of the tunnel family of metal-dependent phosphohydrolases, which is structurally and mechanistically distinct from the human RNA triphosphatase. Using conditional knockdown, we show that TgCet is essential for mRNA capping, and its depletion generates widespread changes in m7G-capped transcripts, resulting in the complete arrest of parasite replication both in culture and in mouse host, thereby protecting them from lethal infection. Finally, the therapeutic potential of TgCet was evaluated using two compounds, Myricetin and 3,4-dicaffeoylquinic acid, reported to inhibit Trypanosoma Cet enzyme. However, only Myricetin demonstrated selective inhibition of TgCet activity and effectively blocked parasite growth in culture. Overall, this study highlights the essential role of TgCet-mediated mRNA capping, establishing RNA triphosphatase as a promising drug target for Toxoplasma infection.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59867-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59867-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59867-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().