tRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptation in Plasmodium falciparum

iScience. 2024 Oct 12;27(11):111167. doi: 10.1016/j.isci.2024.111167. eCollection 2024 Nov 15.

Abstract

An adaptive feature of malaria-causing parasites is the digestion of host hemoglobin (HB) to acquire amino acids (AAs). Here, we describe a link between nutrient availability and translation dependent regulation of gene expression as an adaptive strategy. We show that tRNA expression in Plasmodium falciparum does not match the decoding need expected for optimal translation. A subset of tRNAs decoding AAs that are insufficiently provided by HB are lowly expressed, wherein the abundance of a protein-coding transcript is negatively correlated with the decoding requirement of these tRNAs. Proliferation-related genes have evolved a high requirement of these tRNAs, thereby proliferation can be modulated by repressing protein synthesis of these genes during nutrient stress. We conclude that the parasite modulates translation elongation by maintaining a discordant tRNA profile to exploit variations in AA-composition among genes as an adaptation strategy. This study exemplifies metabolic adaptation as an important driving force for protein evolution.

Keywords: Biochemistry; Biological sciences; Microbial metabolism; Microbial physiology; Microbiology; Natural sciences.