The organization principles of P. falciparum translation initiation features and their potential as drug targets.

ABSTRACT: Plasmodium (P.) falciparum, the deadliest malaria-causing parasite, challenges eradication efforts due to drug resistance. The regulation of mRNA translation as a therapeutic target remains unexplored. Most mRNAs contain unusually long 5'UTR and multiple upstream AUGs. How the parasite overcomes scanning distance and multiple uORF constraints is unknown. We employed the eIF1-eIF4G1 inhibitor i14G1-12, Ribo-seq, TIS-seq, and long-read data on P. falciparum trophozoites. Re-annotation of 5'UTRs, initiation site mapping, and translation efficiency (TE) analysis revealed extended 5'UTR length in hundreds of genes and actively translated uORFs in 81% of mRNAs. Active uORFs were predominantly initiated with AUG lacking specific context, while inactive uORFs were enriched with inhibitory AUG cont

SUBMITTER: Barzilay R 

PROVIDER: S-EPMC12526063 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature