Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/180037
Title: tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum
Authors: Small-Saunders, Jennifer L.
Sinha, Ameya
Bloxham, Talia S.
Hagenah, Laura M.
Sun, Guangxin
Preiser, Peter Rainer
Dedon, Peter C.
Fidock, David A.
Keywords: Medicine, Health and Life Sciences
Issue Date: 2024
Source: Small-Saunders, J. L., Sinha, A., Bloxham, T. S., Hagenah, L. M., Sun, G., Preiser, P. R., Dedon, P. C. & Fidock, D. A. (2024). tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum. Nature Microbiology, 9(6), 1483-1498. https://dx.doi.org/10.1038/s41564-024-01664-3
Project: MOE2018-T2-2-13 
Journal: Nature Microbiology 
Abstract: Plasmodium falciparum artemisinin (ART) resistance is driven by mutations in kelch-like protein 13 (PfK13). Quiescence, a key aspect of resistance, may also be regulated by a yet unidentified epigenetic pathway. Transfer RNA modification reprogramming and codon bias translation is a conserved epitranscriptomic translational control mechanism that allows cells to rapidly respond to stress. We report a role for this mechanism in ART-resistant parasites by combining tRNA modification, proteomic and codon usage analyses in ring-stage ART-sensitive and ART-resistant parasites in response to drug. Post-drug, ART-resistant parasites differentially hypomodify mcm5s2U on tRNA and possess a subset of proteins, including PfK13, that are regulated by Lys codon-biased translation. Conditional knockdown of the terminal s2U thiouridylase, PfMnmA, in an ART-sensitive parasite background led to increased ART survival, suggesting that hypomodification can alter the parasite ART response. This study describes an epitranscriptomic pathway via tRNA s2U reprogramming that ART-resistant parasites may employ to survive ART-induced stress.
URI: https://hdl.handle.net/10356/180037
ISSN: 2058-5276
DOI: 10.1038/s41564-024-01664-3
Schools: School of Biological Sciences 
Organisations: Singapore MIT Alliance for Research and Technology 
Rights: © 2024 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Files in This Item:
File Description SizeFormat 
s41564-024-01664-3.pdf4.84 MBAdobe PDFThumbnail
View/Open

SCOPUSTM   
Citations 50

4
Updated on Dec 6, 2024

Page view(s)

57
Updated on Dec 9, 2024

Download(s)

9
Updated on Dec 9, 2024

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.