Functional characterization of the M6A-dependent translational modulator PfYTH.2 in the human malaria parasite

A Sinha; S Baumgarten; A Distiller; E McHugh; P Chen; M Singh; JM Bryant; J Liang; G Cecere; PC Dedon; PR Preiser; SA Ralph; A Scherf

Journal article

Functional characterization of the M6A-dependent translational modulator PfYTH.2 in the human malaria parasite

A Sinha, S Baumgarten, A Distiller, E McHugh, P Chen, M Singh, JM Bryant, J Liang, G Cecere, PC Dedon, PR Preiser, SA Ralph, A Scherf

Mbio | AMER SOC MICROBIOLOGY | Published : 2021

DOI: 10.1128/mBio.00661-21

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Abstract

Posttranscriptional regulation of gene expression is central to the development and replication of the malaria parasite, Plasmodium falciparum, within its human host. The timely coordination of RNA maturation, homeostasis, and protein synthesis relies on the recruitment of specific RNA-binding proteins to their cognate target mRNAs. One possible mediator of such mRNA-protein interactions is the N6-methylation of adenosines (m6A), a prevalent mRNA modification of parasite mRNA transcripts. Here, we used RNA protein pulldowns, RNA modification mass spectrometry, and quantitative proteomics to identify two P. falciparum YTH domain proteins (PfYTH.1 and PfYTH.2) as m6A-binding proteins during pa..

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University of Melbourne Researchers

Emma McHugh Author

Stuart Ralph Author

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Grants

Awarded by National Research Foundation Singapore

Funding Acknowledgements

This work was supported by a European Research Council Advanced Grant (PlasmoSilencing 670301) and the French Parasitology consortium ParaFrap (ANR-11-LABX0024) awarded to A. Scherf. S.B. is supported by an EMBO Advanced Long-Term Fellowship (aALTF 632-2018). P.R.P., P.C.D., J.L., and A. Sinha were supported by the National Research Foundation Singapore under its Singapore-MIT Alliance for Research and Technology (SMART) Centre, Antimicrobial Resistance IRG and Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2018-T2-2-131). A. Sinha and J.L. acknowledge support from the Singapore-MIT Alliance (SMA) Graduate Fellowship. Proteomics work was performed in part in the Center for Environmental Health Sciences BioCore, which is supported by Center grant P30-ES002109 from the National Institute of Environmental Health Sciences. We also acknowledge Peiying Ho and Tan Tse Mien for providing support at SMART laboratories in Singapore. G.C. and M.S. were funded by a European Research Council (ERC) Starting Grant (ERC-StG-679243). Work on this project in the laboratory of S.A.R. is funded by a grant from the Australian National Health and Medical Research Council (1165354) and by a grant from the Australian Research Council (DP160100389).